Human Disease Model Report: cancer, neural stem cell, disruption of asymmetric division

General Information

Name

cancer, neural stem cell, disruption of asymmetric division

FlyBase ID

FBhh0000954

Disease Ontology Term

brain cancer

Parent Disease

OMIM

Overview

Asymmetric division is a critical step in the differentiation of post-embryonic stem cells during which each stem cell generates one self-renewing and one differentiating daughter cell. Mutations in Drosophila genes that disrupt the process of asymmetric division have been studied as models of neural-stem-cell derived cancers. Genes studied include numb, mira, pros, pins, brat, lncRNA:cherub, l(3)mbt, and Arp8.

Loss-of-function mutations that affect normal neuroblast differentiation in Drosophila often result in conspicuous phenotypes of overproliferation and tumorous expansion of the brain at the larval stage. In brat or pros mutants, both daughter cells of the normally asymmetric division grow and behave like neuroblasts, leading to the formation of larval brain tumors comprised primarily of neuroblast-like cells. A sensitive test of neoplastic transformation is transplantation of potential tumorous cells into the abdomen of adult hosts; cells are observed for proliferation and invasive behaviors. One of the earliest genes characterized in this transplantation assay was brat. Homozygous loss-of-function mutations of numb, mira, pros, and pins have also been tested in this assay; larval brain tissue carrying neuroblasts with any of these mutations grew to more than 100 times their initial size, invading other tissues and killing the hosts in 2 weeks. The tumors became immortal and could be re-transplanted into new hosts for years.

In a study of genes upregulated in brat tumor neuroblasts, the long non-coding RNA lncRNA:cherub was identified. During normal neuroblast mitosis lncRNA:cherub is asymmetrically distributed. Loss or knockdown of lncRNA:cherub suppresses the brat tumor phenotype.

Using Ras85D^V12 scrib mutant clones as a sensitized genetic background, an RNAi screen in larval brain neuroblasts identified potential asymmetric cell division regulators that also act as tumor suppressor genes. The Arp8 gene, othologous to human ACTR8, was identified in this screen and has been characterized further.

See also reports for well-studied disease models using specific genes, 'cancer, neural stem cell, TRIM2,3-related' (FBhh0000772, using the fly gene brat) and 'cancer, neural stem cell, L3MBTL-related' (FBhh0000773, using the fly gene l(3)mbt).

[updated Mar. 2022 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, neural stem cell, disruption of asymmetric division

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

Disease synonyms

Search term: metastatic phenotype(s)

Search term: neoplastic phenotype(s)

Related Diseases

Related human health report(s)

cancer, neural stem cell, L3MBTL-related

cancer, neural stem cell, TRIM2,3-related

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (8)

Dmel\numb

Gene Snapshot

numb (numb) encodes a membrane-associated inhibitor of Notch signaling. It controls neuroblast and sense organ precursor asymmetric division. It is asymmetrically localized during mitosis and segregates exclusively to one of two daughter cells. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

NTCH-N

Comments on ortholog(s)

High-scoring ortholog of human NUMB and NUMBL (1 Drosophila to 2 human). Dmel\numb shares 39-41% identity and 49-51% similarity with the human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\mira

Gene Snapshot

miranda (mira) encodes a cytoplasmic and cortical scaffolding protein that binds the products of pros, stau and brat. It is asymmetrically localized to the basal cortex during neuroblast asymmetric cell division, resulting in its partioning into GMC daughter cells, where it is degraded and releases its cargo proteins. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

No gene orthologous to mira has been identified in human.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\pros

Gene Snapshot

prospero (pros) encodes a protein that promotes the expression of neural differentiation genes and represses neuroblast stem cell identity genes and cell cycle proliferation genes; it is also important for astrocyte development. The product of pros is asymmetrically localized to the basal cortex during neuroblast asymmetric cell division, resulting in its partioning into GMC daughter cells, where it translocates into the nucleus. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

PROS

Comments on ortholog(s)

Moderate-scoring ortholog of human PROX1 and PROX2 (1 Drosophila to 2 human). Dmel\pros shares 24-29% identity and 35-41% similarity with the human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\pins

Gene Snapshot

partner of inscuteable (pins) encodes a GDP-dissociation inhibitor involved in asymmetric cell division and mitotic spindle orientation. [Date last reviewed: 2019-06-13]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human GPSM2 and GPMS1 (1 Drosophila to 2 human). Dmel\pins shares 45-47% identity and 60-63% similarity with the human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\brat

Gene Snapshot

brain tumor (brat) encodes a tumor suppressor that regulates proliferation in the brain. During neural stem cell division, it segregates into one daughter cell where it inhibits protein translation, preventing self-renewal and inducing differentiation. It also acts during oogenesis where it interacts with the products of nanos and pum to suppress hb translation. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Low-scoring ortholog of human TRIM3 and TRIM2 (2 Drosophila to 2 human). Dmel\brat shares 23-25% identity and 39-41% similarity with the human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\l(3)mbt

Gene Snapshot

lethal (3) malignant brain tumor (l(3)mbt) encodes a tumor suppressor protein regulating proliferation in the brain, particularly the optic lobes. The proposed functions of the product of l(3)mbt include histone compaction, establishment of chromatin insulators, regulation of the Hippo pathway and repression of the germ line program in somatic cells. [Date last reviewed: 2019-09-26]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-scoring ortholog of human L3MBTL3, L3MBTL4, and L3MBTL1 (1 Drosophila to 3 human). Dmel\l(3)mbt shares 28-31% identity and 42-46% similarity with the human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\lncRNA:cherub

Gene Snapshot

Contributions welcome

Molecular function (GO)

protein-macromolecule adaptor activity

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\Arp8

Gene Snapshot

Contributions welcome

Molecular function (GO)

mRNA binding

Cellular component (GO)

Gene Groups / Pathways

ARP
INO80

Comments on ortholog(s)

High-scoring ortholog of human ACTR8 (1 Drosophila to 1 human).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (109 groups)

numb

protein-protein

Interacting group

Assay

References

numb

anti tag coimmunoprecipitation, anti tag western blot

(Shan et al., 2018)

numb - AP-1γ

anti tag coimmunoprecipitation, western blot

(Cotton et al., 2013)

numb - AP-2α

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, pull down, anti tag western blot, autoradiography

(Cotton et al., 2013, Song and Lu, 2012, Wirtz-Peitz et al., 2008, Bhalerao et al., 2005, Berdnik et al., 2002)

numb - aPKC

pull down, western blot

(Wirtz-Peitz et al., 2008)

numb - baz

pull down, western blot

(Wirtz-Peitz et al., 2008)

numb - Crmp

anti tag coimmunoprecipitation, anti tag western blot

(Jauffred et al., 2013)

numb - Dap160

pull down, western blot

(Tang et al., 2005)

numb - Dronc

anti tag coimmunoprecipitation, anti tag western blot

(Ouyang et al., 2011)

numb - Eps-15

pull down, western blot, two hybrid

(Tang et al., 2005)

numb - mira

pull down, autoradiography

(Shen et al., 1998, Shen et al., 1997)

numb - mol

pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, lambda phage display, fluorescence polarization spectroscopy, predetermined participant

(Qin et al., 2004)

numb - N

pull down, autoradiography, two hybrid

(Guo et al., 1996)

numb - Nak

pull down, molecular weight estimation by staining, anti tag coimmunoprecipitation, western blot, cosedimentation, molecular weight, fluorescence polarization spectroscopy, predetermined participant, two hybrid, nuclear magnetic resonance, autoradiography

(Shan et al., 2018, Tang et al., 2005, Zwahlen et al., 2000, Chien et al., 1998, Li et al., 1998)

numb - par-6

pull down, western blot

(Wirtz-Peitz et al., 2008)

numb - Past1

pull down, anti tag western blot, phage display, tag visualisation

(Smith et al., 2004)

numb - pon

two hybrid, anti tag coimmunoprecipitation, anti tag western blot, cosedimentation, molecular weight, pull down, anti bait coimmunoprecipitation, western blot, isothermal titration calorimetry, predetermined participant, x-ray crystallography, molecular weight estimation by staining

(Shan et al., 2018, Ouyang et al., 2011, Bhalerao et al., 2005, Lu et al., 1998)

numb - spdo

anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot

(Cotton et al., 2013, Song and Lu, 2012, Tong et al., 2010, Bhalerao et al., 2005, Hutterer and Knoblich, 2005, O'Connor-Giles and Skeath, 2003)

RNA-RNA

Interacting group

Assay

References

numb - mir-ban

luminiscence technology, necessary binding region

(Wu et al., 2017)

mira

protein-protein

Interacting group

Assay

References

mira

detection by mass spectrometry, comigration in gel electrophoresis, molecular weight estimation by staining, protein cross-linking with a bifunctional reagent, anti tag coimmunoprecipitation, western blot

(Ramat et al., 2017, Yousef et al., 2008)

mira - aPKC

anti bait coimmunoprecipitation, western blot, enzymatic study, autoradiography, pull down, anti tag coimmunoprecipitation, anti tag western blot

(Atwood and Prehoda, 2009, Wirtz-Peitz et al., 2008)

mira - baz

pull down, anti tag western blot

(Wirtz-Peitz et al., 2008)

mira - brat

molecular sieving, molecular weight estimation by staining, two hybrid, pull down, isothermal titration calorimetry, predetermined participant, anti tag coimmunoprecipitation, anti tag western blot

(Liu et al., 2019, Jia et al., 2015, Komori et al., 2014, Lee et al., 2006)

mira - cup

two hybrid, pull down, western blot

(Piccioni et al., 2009)

mira - flfl

pull down, Identification by mass spectrometry, anti tag coimmunoprecipitation, western blot, two hybrid, autoradiography

(Karman et al., 2020, Sousa-Nunes et al., 2009)

mira - gdrd

two hybrid

(Hu et al., 2017.6.13)

mira - insc

pull down, autoradiography

(Shen et al., 1998)

mira - jar

anti bait coimmunoprecipitation, western blot, pull down, anti tag western blot, peptide massfingerprinting, autoradiography

(Finan et al., 2011, Petritsch et al., 2003)

mira - numb

pull down, autoradiography

(Shen et al., 1998, Shen et al., 1997)

mira - par-6

pull down, western blot

(Wirtz-Peitz et al., 2008)

mira - pon

anti tag coimmunoprecipitation, western blot

(Lu et al., 1998)

mira - pros

pull down, autoradiography, two hybrid, western blot, anti bait coimmunoprecipitation

(Wirtz-Peitz et al., 2008, Petritsch et al., 2003, Shen et al., 1998, Ikeshima-Kataoka et al., 1997, Shen et al., 1997)

mira - stau

x-ray crystallography, predetermined participant, anti tag coimmunoprecipitation, anti tag western blot, isothermal titration calorimetry, molecular sieving, pull down, autoradiography, two hybrid, anti bait coimmunoprecipitation, western blot

(Jia et al., 2015, Petritsch et al., 2003, Schuldt et al., 1998, Shen et al., 1998)

mira - zip

anti bait coimmunoprecipitation, peptide massfingerprinting

(Petritsch et al., 2003)

RNA-protein

Interacting group

Assay

References

mira

(Ramat et al., 2017, Yousef et al., 2008)

mira - pros

pull down, autoradiography, two hybrid, western blot, anti bait coimmunoprecipitation

(Wirtz-Peitz et al., 2008, Petritsch et al., 2003, Shen et al., 1998, Ikeshima-Kataoka et al., 1997, Shen et al., 1997)

pros

protein-protein

Interacting group

Assay

References

pros

anti tag coimmunoprecipitation, anti tag western blot

(Liu et al., 2020)

pros - abd-A

bimolecular fluorescence complementation, fluorescence microscopy

(Bischof et al., 2018)

pros - C15

two hybrid array

(Shokri et al., 2019)

pros - Clbn

two hybrid, pull down, autoradiography

(Bi et al., 2005)

pros - CtBP

two hybrid array

(Shokri et al., 2019)

pros - CycE

anti tag coimmunoprecipitation, western blot

(Berger et al., 2010)

pros - L

two hybrid array

(Shokri et al., 2019)

pros - mira

pull down, autoradiography, two hybrid, western blot, anti bait coimmunoprecipitation

(Wirtz-Peitz et al., 2008, Petritsch et al., 2003, Shen et al., 1998, Ikeshima-Kataoka et al., 1997, Shen et al., 1997)

pros - spoon

anti bait coimmunoprecipitation, western blot

(Tripathi et al., 2017)

RNA-protein

Interacting group

Assay

References

pros - Caper

anti bait coimmunoprecipitation, full identification by RNA sequencing, anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Titus et al., 2023)

pros - Hrb87F

pull down, Identification by mass spectrometry

(Borah et al., 2009)

pros - Hrb98DE

pull down, Identification by mass spectrometry

(Borah et al., 2009)

pros - kin17

anti tag coimmunoprecipitation, reverse transcription pcr

(Connell et al., 2024)

pros - mira

pull down, autoradiography, two hybrid, western blot, anti bait coimmunoprecipitation

(Wirtz-Peitz et al., 2008, Petritsch et al., 2003, Shen et al., 1998, Ikeshima-Kataoka et al., 1997, Shen et al., 1997)

pros - stau

pull down, autoradiography, anti tag coimmunoprecipitation, partial DNA sequence identification by hybridization, anti bait coimmunoprecipitation

(Laver et al., 2013, Li et al., 1997)

pros - Syp

anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Samuels et al., 2020)

pins

protein-protein

Interacting group

Assay

References

pins - aurA

enzymatic study, autoradiography

(Johnston et al., 2009)

pins - cnk

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

pins - cno

anti bait coimmunoprecipitation, western blot, pull down

(Wee et al., 2011, Speicher et al., 2008)

pins - dlg1

anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot, two hybrid, molecular weight estimation by staining, anti bait coimmunoprecipitation

(Mauser and Prehoda, 2012, Siegrist and Doe, 2005, Bellaiche et al., 2001)

pins - dos

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

pins - drk

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

pins - Gαi

two hybrid, anti bait coimmunoprecipitation, western blot, pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot

(Yoshiura et al., 2012, Kopein and Katanaev, 2009, Bowman et al., 2006, Hampoelz et al., 2005, Wang et al., 2005, Yu et al., 2005, Schaefer et al., 2001, Parmentier et al., 2000, Schaefer et al., 2000)

pins - Gαo

two hybrid, fluorescent resonance energy transfer, pull down, western blot, autoradiography, experimental knowledge based, anti tag coimmunoprecipitation, anti bait coimmunoprecipitation

(Lüchtenborg et al., 2015, Yoshiura et al., 2012, Guruharsha et al., 2011, Kopein and Katanaev, 2009, Katanaev and Tomlinson, 2006, Schaefer et al., 2000)

pins - gig

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

pins - hts

pull down, molecular weight estimation by staining

(Parra et al., 2023)

pins - insc

pull down, molecular weight estimation by staining, autoradiography, anti tag coimmunoprecipitation, western blot, x-ray crystallography, anti bait coimmunoprecipitation, molecular sieving, two hybrid, static light scattering, molecular weight, peptide massfingerprinting

(Parra et al., 2023, Culurgioni et al., 2018, Januschke et al., 2013, Mauser and Prehoda, 2012, Culurgioni et al., 2011, Schaefer et al., 2000, Yu et al., 2000)

pins - Lkb1

anti bait coimmunoprecipitation, western blot

(Blumer et al., 2003)

pins - mud

anti tag coimmunoprecipitation, anti tag western blot, fluorescence polarization spectroscopy, predetermined participant, pull down, molecular weight estimation by staining, anti bait coimmunoprecipitation, western blot, molecular sieving, molecular weight estimation by coomasie staining, coimmunoprecipitation, molecular weight estimation by silver staining, Identification by mass spectrometry, autoradiography

(Mauser and Prehoda, 2012, Smith and Prehoda, 2011, Wang et al., 2011, Wee et al., 2011, Nipper et al., 2007, Bowman et al., 2006, Izumi et al., 2006, Siller et al., 2006)

pins - RasGAP1

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

pins - RhoGAP18B

experimental knowledge based

(Guruharsha et al., 2011)

pins - ric8a

pull down, western blot, anti bait coimmunoprecipitation

(Wang et al., 2005)

pins - Tsc1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

brat

protein-protein

Interacting group

Assay

References

brat

x-ray crystallography

(Liu et al., 2019)

brat - AGO1

anti bait coimmunoprecipitation, peptide massfingerprinting, two hybrid, bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot, western blot

(Malik et al., 2017, Neumuller et al., 2008)

brat - bam

bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot, western blot, two hybrid

(Malik, 2021, Malik et al., 2017)

brat - eIF4EHP

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot

(Cho et al., 2006)

brat - mira

molecular sieving, molecular weight estimation by staining, two hybrid, pull down, isothermal titration calorimetry, predetermined participant, anti tag coimmunoprecipitation, anti tag western blot

(Liu et al., 2019, Jia et al., 2015, Komori et al., 2014, Lee et al., 2006)

brat - nanos

anti tag coimmunoprecipitation, quantitative reverse transcription pcr, two hybrid

(Malik et al., 2020, Sonoda and Wharton, 2001)

brat - pum

three hybrid, molecular sieving, molecular weight estimation by staining, pull down, western blot, anti tag western blot, transcriptional complementation assay

(Loedige et al., 2014, Kadyrova et al., 2007, Cho et al., 2006, Edwards et al., 2001, Sonoda and Wharton, 2001)

brat - sstn

anti tag coimmunoprecipitation, peptide massfingerprinting

(Liu et al., 2015)

brat - stau

pull down, molecular weight estimation by staining, anti tag coimmunoprecipitation, primer specific pcr

(Jia et al., 2015, Loedige et al., 2015)

brat - Sxl

bimolecular fluorescence complementation, fluorescence microscopy, two hybrid, anti tag coimmunoprecipitation, anti tag western blot

(Malik et al., 2017)

brat - Tis11

anti tag coimmunoprecipitation, anti tag western blot

(Komori et al., 2018)

RNA-protein

Interacting group

Assay

References

brat - aub

iclip, partial RNA sequence identification

(Ma et al., 2017)

brat - chinmo

anti tag coimmunoprecipitation, primer specific pcr

(Loedige et al., 2015)

brat - Corin

anti tag coimmunoprecipitation, primer specific pcr

(Loedige et al., 2015)

brat - dpn

electrophoretic mobility shift assay, autoradiography, anti tag coimmunoprecipitation, primer specific pcr

(Reichardt et al., 2018, Loedige et al., 2015)

brat - elav

anti bait coimmunoprecipitation, primer specific pcr

(Hilgers et al., 2012)

brat - hb

microscale thermophoresis, predetermined participant, anti tag coimmunoprecipitation, quantitative reverse transcription pcr, nucleic acid uv cross-linking assay, Identification by mass spectrometry, molecular sieving, static light scattering, electrophoretic mobility shift assay, autoradiography

(Malik et al., 2020, Malik et al., 2019, Loedige et al., 2014)

brat - klu

electrophoretic mobility shift assay, autoradiography, anti tag coimmunoprecipitation, primer specific pcr

(Loedige et al., 2015)

brat - kni

electrophoretic mobility shift assay, autoradiography, anti tag coimmunoprecipitation, primer specific pcr

(Loedige et al., 2015)

brat - Mad

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Malik et al., 2019)

brat - Myc

anti bait coimmunoprecipitation, quantitative reverse transcription pcr, anti tag coimmunoprecipitation, primer specific pcr

(Malik, 2021, Loedige et al., 2015)

brat - nanos

anti tag coimmunoprecipitation, quantitative reverse transcription pcr, two hybrid

(Malik et al., 2020, Sonoda and Wharton, 2001)

brat - orb2

pull down, western blot

(Mastushita-Sakai et al., 2010)

brat - par-6

anti tag coimmunoprecipitation, primer specific pcr

(Loedige et al., 2015)

brat - Pc

anti tag coimmunoprecipitation, primer specific pcr

(Loedige et al., 2015)

brat - piwi

anti bait coimmunoprecipitation, northern blot

(Saito et al., 2009)

brat - Sirt1

anti tag coimmunoprecipitation, primer specific pcr

(Loedige et al., 2015)

brat - stau

pull down, molecular weight estimation by staining, anti tag coimmunoprecipitation, primer specific pcr

(Jia et al., 2015, Loedige et al., 2015)

brat - w

anti tag coimmunoprecipitation, primer specific pcr

(Loedige et al., 2015)

brat - zld

electrophoretic mobility shift assay, autoradiography, anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Reichardt et al., 2018)

l(3)mbt

protein-protein

Interacting group

Assay

References

l(3)mbt - Ada2b

anti tag coimmunoprecipitation, peptide massfingerprinting

(Weake et al., 2011)

l(3)mbt - Atac3

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based, anti bait coimmunoprecipitation, Identification by mass spectrometry

(Yamamoto-Matsuda et al., 2022, Rhee et al., 2014)

l(3)mbt - CoRest

molecular sieving, western blot, anti tag coimmunoprecipitation, anti bait coimmunoprecipitation, Identification by mass spectrometry, ion exchange chromatography

(Mačinković et al., 2019, Meier et al., 2012)

l(3)mbt - Cp190

two hybrid

(Melnikova et al., 2019)

l(3)mbt - E2f1

anti tag coimmunoprecipitation, western blot

(Lu et al., 2007)

l(3)mbt - HDAC1

coimmunoprecipitation, western blot

(Scharf et al., 2009)

l(3)mbt - His3.3A

anti bait coimmunoprecipitation, Identification by mass spectrometry

(Yamamoto-Matsuda et al., 2022)

l(3)mbt - His4

pull down, western blot

(Scharf et al., 2009)

l(3)mbt - indra

anti bait coimmunoprecipitation, Identification by mass spectrometry

(Yamamoto-Matsuda et al., 2022)

l(3)mbt - Lint-1

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, affinity technology, peptide massfingerprinting, pull down, autoradiography, experimental knowledge based, molecular sieving, ion exchange chromatography, Identification by mass spectrometry

(Yamamoto-Matsuda et al., 2022, Rhee et al., 2014, Meier et al., 2012)

l(3)mbt - Lint-O

anti bait coimmunoprecipitation, western blot, anti tag western blot, Identification by mass spectrometry, anti tag coimmunoprecipitation

(Yamamoto-Matsuda et al., 2022)

l(3)mbt - mip120

pull down, autoradiography

(Blanchard et al., 2014)

l(3)mbt - Polr2C

anti bait coimmunoprecipitation, Identification by mass spectrometry

(Yamamoto-Matsuda et al., 2022)

l(3)mbt - prod

anti bait coimmunoprecipitation, Identification by mass spectrometry

(Yamamoto-Matsuda et al., 2022)

l(3)mbt - Scm

tandem affinity purification, Identification by mass spectrometry

(Kang et al., 2015)

l(3)mbt - Su(H)

pull down, autoradiography

(Xu et al., 2017)

lncRNA:cherub

RNA-protein

Interacting group

Assay

References

lncRNA:cherub - stau

anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Landskron et al., 2018)

lncRNA:cherub - Syp

anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Landskron et al., 2018)

Arp8

protein-protein

Interacting group

Assay

References

Arp8 - pho

anti tag coimmunoprecipitation, peptide massfingerprinting

(Klymenko et al., 2006)

Alleles Reported to Model Human Disease (Disease Ontology) (30 alleles)

numb

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

numb⁰³²³⁵

model of brain cancer

CEA

(Caussinus and Gonzalez, 2005)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

numb^PTB.UAS.GFP

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

ameliorates brain cancer

modeled by aurA⁸⁸³⁹

(Wang et al., 2006)

mira

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

mira^ZZ176

model of brain cancer

CEA

(Caussinus and Gonzalez, 2005)

model of cancer

CEA

(Janic et al., 2010)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

mira^HMS00347

exacerbates central nervous system cancer

modeled by N^UAS.icd

(Zacharioudaki et al., 2016)

pros

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

pros¹⁷

model of brain cancer

CEA

(Narbonne-Reveau et al., 2016, Bello et al., 2006, Betschinger et al., 2006, Caussinus and Gonzalez, 2005)

model of cancer

CEA

(Janic et al., 2010)

pros^KK109284

model of brain cancer

CEA

(Narbonne-Reveau et al., 2016)

CEA with chinmo^HMS00036

(Narbonne-Reveau et al., 2016)

CEA with chinmo^UAS.fl

(Narbonne-Reveau et al., 2016)

pros^JF02308

model of brain cancer

CEA

(Gaultier et al., 2022, Narbonne-Reveau et al., 2016)

Modifiers Based on Experimental Evidence ( 5 )

Allele

Disease

Interaction

References

pros^HMJ02107

ameliorates Machado-Joseph disease

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Han et al., 2020)

pros¹⁷

exacerbates chronic myeloid leukemia

modeled by Hsap\ABL1::Hsap\BCR^UAS.cBa

(Bernardoni et al., 2019)

ameliorates non-syndromic X-linked intellectual disability

modeled by Acsl⁰⁵⁸⁴⁷, Acsl⁸

(Jia et al., 2019)

exacerbates syndromic intellectual disability

modeled by Kdm5¹⁴⁰

(Hatch et al., 2021)

pros^UAS.cMa

ameliorates brain cancer

modeled by brat¹¹

(Bello et al., 2006)

pros^KK109284

model of brain cancer

is ameliorated by Imp^GD9232

(Narbonne-Reveau et al., 2016)

pros^JF02308

model of brain cancer

is ameliorated by E(z)^KK102729

(Gaultier et al., 2022)

is ameliorated by Hsap\H3-3A^{K27M.UAS.Tag:FLAG,Tag:HA}

(Gaultier et al., 2022)

is ameliorated by Psc^JF01395

(Gaultier et al., 2022)

is ameliorated by Set1^HMS00581

(Gaultier et al., 2022)

is ameliorated by Su(z)12^JF01706

(Gaultier et al., 2022)

is ameliorated by abd-A^UAS.Tag:HA

(Gaultier et al., 2022)

is exacerbated by cas^UAS.cKa

(Gaultier et al., 2022)

is ameliorated by E(z)^JF02826

(Gaultier et al., 2022)

is exacerbated by esc^GD1240

(Gaultier et al., 2022)

is ameliorated by trr^JF03242

(Gaultier et al., 2022)

is ameliorated by trx^KK100756

(Gaultier et al., 2022)

pins

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

pins^P62

model of brain cancer

CEA with pins^P89

(Caussinus and Gonzalez, 2005)

model of cancer

CEA with pins^P89

(Janic et al., 2010)

pins^P89

model of brain cancer

CEA with pins^P62

(Caussinus and Gonzalez, 2005)

model of cancer

CEA with pins^P62

(Janic et al., 2010)

Modifiers Based on Experimental Evidence ( 0 )

Allele

Disease

Interaction

References

brat

Models Based on Experimental Evidence ( 9 )

Allele

Disease

Evidence

References

brat^HMS01121

model of cancer

CEA

(Hussain et al., 2017)

model of brain cancer

CEA

(Diaz et al., 2024, Hofstetter et al., 2024)

brat¹¹

model of brain cancer

CEA

(Narbonne-Reveau et al., 2016, Bello et al., 2006, Lee et al., 2006)

CEA with chinmo¹

(Narbonne-Reveau et al., 2016)

brat¹⁴

model of brain cancer

CEA with brat¹⁸

(Beaucher et al., 2007)

brat¹⁸

model of brain cancer

CEA with brat¹⁴

(Beaucher et al., 2007)

brat^2L-192-9

model of brain cancer

CEA

(Betschinger et al., 2006)

brat^k06028

model of brain cancer

CEA

(Diaz et al., 2024, Molnar et al., 2019, Rossi et al., 2018, Janic et al., 2010)

brat^KK113206

model of brain cancer

CEA

(Rebelo and Homem, 2023, Jiang et al., 2018, Loewen et al., 2018)

model of neurodegenerative disease

CEA

(Loewen et al., 2018)

brat^RNAi.UAS.cUa

model of brain cancer

CEA

(Mukherjee et al., 2018)

brat^chs

model of neurodegenerative disease

CEA

(Tafesh-Edwards et al., 2023, Loewen et al., 2018)

model of brain cancer

CEA

(Loewen et al., 2018)

Modifiers Based on Experimental Evidence ( 8 )

Allele

Disease

Interaction

References

brat^HMS01121

model of cancer

is ameliorated by Pepck1^GD9451

(Hussain et al., 2017)

is ameliorated by Mfe2^KK101732

(Hussain et al., 2017)

is ameliorated by Gpdh1^GD14102

(Hussain et al., 2017)

is ameliorated by Mdh1^GD11625

(Hussain et al., 2017)

is ameliorated by Men^GL01234

(Hussain et al., 2017)

model of brain cancer

is ameliorated by Spt5^HMS00153

(Hofstetter et al., 2024)

is ameliorated by Heatr1^GD7096

(Diaz et al., 2024)

is ameliorated by Myc^GD1419

(Diaz et al., 2024)

brat¹

exacerbates viral infectious disease

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates infectious mononucleosis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates Epstein-Barr virus hepatitis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

brat¹¹

model of brain cancer

is ameliorated by pros^UAS.cMa

(Bello et al., 2006)

brat^k06028

exacerbates viral infectious disease

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates infectious mononucleosis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates Epstein-Barr virus hepatitis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

brat^UAS.Tag:MYC

ameliorates brain cancer

modeled by brat^chs

(Loewen et al., 2018)

ameliorates neurodegenerative disease

modeled by brat^chs

(Loewen et al., 2018)

brat^KK113206

model of brain cancer

is ameliorated by EcR^B1.UAS

(Jiang et al., 2018)

is ameliorated by mir-let7^UAS.cCa

(Jiang et al., 2018)

is ameliorated by CD98hc^HMC04939

(Rebelo and Homem, 2023)

is ameliorated by CD98hc^KK104374

(Rebelo and Homem, 2023)

is ameliorated by CG1607^HMC04991

(Rebelo and Homem, 2023)

is ameliorated by JhI-21^HMS02271

(Rebelo and Homem, 2023)

is ameliorated by MFS3^KK110254

(Rebelo and Homem, 2023)

is ameliorated by Myc^KK103869

(Rebelo and Homem, 2023)

is ameliorated by Tret1^HMS02573

(Rebelo and Homem, 2023)

is ameliorated by chk^GD1829

(Rebelo and Homem, 2023)

is ameliorated by gb^GD315

(Rebelo and Homem, 2023)

is ameliorated by hrm^HMC03642

(Rebelo and Homem, 2023)

is ameliorated by mnd^HMC05214

(Rebelo and Homem, 2023)

is ameliorated by CG30394^GD2127

(Rebelo and Homem, 2023)

is ameliorated by CG5535^KK100907

(Rebelo and Homem, 2023)

is ameliorated by Scsα1^KK102542

(Rebelo and Homem, 2023)

brat^RNAi.UAS.cUa

model of brain cancer

is ameliorated by Cdk5α^RNAi.UAS.cUa

(Mukherjee et al., 2018)

is ameliorated by Eip63E^RNAi.UAS.cUa

(Mukherjee et al., 2018)

is ameliorated by S6k^RNAi.UAS.cUa

(Mukherjee et al., 2018)

is ameliorated by Cdk5^RNAi.UAS.cUa

(Mukherjee et al., 2018)

is ameliorated by S6k^RNAi.UAS.cUa

(Mukherjee et al., 2018)

brat^chs

model of brain cancer

is exacerbated by CG15864^MB04166

(Loewen et al., 2018)

is ameliorated by brat^UAS.Tag:MYC

(Loewen et al., 2018)

model of neurodegenerative disease

is exacerbated by CG15864^MB04166

(Loewen et al., 2018)

is ameliorated by brat^UAS.Tag:MYC

(Loewen et al., 2018)

l(3)mbt

Models Based on Experimental Evidence ( 6 )

Allele

Disease

Evidence

References

l(3)mbt^RNAi.UAS

model of brain cancer

CEA

(Richter et al., 2011)

l(3)mbt^E2

model of brain cancer

CEA with l(3)mbt^ts1

(Molnar et al., 2019)

CEA

(Janic et al., 2010)

l(3)mbt^GM76

model of brain cancer

CEA

(Richter et al., 2011)

l(3)mbt^ts1

model of brain cancer

CEC with l(3)mbt^GD4370

(Climent-Cantó et al., 2022)

CEA

(Molnar et al., 2019, Rossi et al., 2018, Rossi et al., 2017, Richter et al., 2011, Janic et al., 2010, Gateff et al., 1993)

CEA with l(3)mbt^E2

(Molnar et al., 2019)

l(3)mbt^GD4370

model of brain cancer

CEC with l(3)mbt^ts1

(Climent-Cantó et al., 2022)

l(3)mbt^KK100812

model of brain cancer

CEA

(Meier et al., 2012)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

l(3)mbt^GM76

model of brain cancer

is ameliorated by ex^UAS.cBa

(Richter et al., 2011)

is ameliorated by yki^B5

(Richter et al., 2011)

l(3)mbt^ts1

model of brain cancer

is ameliorated by Phf7^ΔN2

(Molnar et al., 2019)

is ameliorated by aub^QC42

(Janic et al., 2010)

is ameliorated by nanos¹⁷

(Janic et al., 2010)

is ameliorated by piwi¹

(Janic et al., 2010)

is ameliorated by vas^PH165

(Janic et al., 2010)

is ameliorated by CG32694^KK112598

(Rossi et al., 2017)

is ameliorated by Nipped-A^GD9847

(Rossi et al., 2017)

is ameliorated by Cul2^KK100540

(Rossi et al., 2017)

is exacerbated by halo^KK106139

(Rossi et al., 2017)

is ameliorated by Tctp^RNAi.UAS

(Rossi et al., 2017)

is ameliorated by mei-W68^KK109695

(Rossi et al., 2017)

is ameliorated by tud^KK101221

(Rossi et al., 2017)

l(3)mbt^HMS01466

ameliorates amyotrophic lateral sclerosis type 1

modeled by Hsap\SOD1^A4V.UAS

(Lu et al., 2019)

ameliorates C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis

modeled by Zzzz\poly-GR^PO-100.UAS

(Lu et al., 2019)

modeled by Zzzz\poly-PR^PO-100.UAS

(Lu et al., 2019)

Arp8

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Arp8^KK108716

exacerbates brain cancer

modeled by Ras85D^V12.cUa.UAS, scrib⁶⁷³

(Manzanero-Ortiz et al., 2021)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

numb^PTB.UAS.GFP

P{UAS-numb.PTB.GFP}

w^*; P{UAS-numb.PTB.GFP}2/CyO

brat^UAS.Tag:MYC

P{UAS-brat.myc}

w^*; wg^Sp-1/CyO, P{ActGFP}JMR1; P{UAS-brat.myc}3/TM2

pros^UAS.cMa

P{UAS-pros.17K-2}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

y¹ v¹; P{TRiP.JF01720}attP2/TM3, Sb¹

y¹ v¹; P{TRiP.JF01695}attP2

numb^HMS01459

P{TRiP.HMS01459}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01459}attP2

numb^NIG.3779R

P{NIG.3779R}

numb^{RNAi.UAS.THU1674}

P{UAS-numb.RNAi.THU1674}

brat^{miR.FOFO1.0.Act5C}

P{Act5C(FOFO1.0)brat^miRsGAL4^miRs}

brat^{miR.FOFO2.0.Act5C}

P{Act5C(FOFO2.0)brat^miRsGAL4^miRs}

w^*; P{Act5C(FOFO2.0)brat^miRsGAL4^miRs}attP40/CyO, P{Dfd-EYFP}2

brat^GD7073

P{GD7073}

w¹¹¹⁸ P{GD7073}v31333

y¹ v¹; P{TRiP.HM05078}attP2

brat^HMS01121

P{TRiP.HMS01121}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01121}attP2

w¹¹¹⁸; P{GD1596}v51484/CyO

mira^HMS00347

P{TRiP.HMS00347}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00347}attP2

w¹¹¹⁸; P{GD4370}v13994/TM3

y¹ v¹; P{TRiP.JF02913}attP2

l(3)mbt^HMS01466

P{TRiP.HMS01466}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01466}attP2/TM3, Sb¹

w¹¹¹⁸; P{GD11737}v27486/TM3

pins^JF02450

P{TRiP.JF02450}

y¹ v¹; P{TRiP.JF02450}attP2

pins^HMS01462

P{TRiP.HMS01462}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01462}attP2

pins^GL00622

P{TRiP.GL00622}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00622}attP40

pins^HMJ21351

P{TRiP.HMJ21351}

y¹ v¹; P{TRiP.HMJ21351}attP40

pins^VSH330242

P{VSH330242}

P{VSH330242}attP40

pros^{miR.FOFO1.0.Act5C}

P{Act5C(FOFO1.0)pros^miRsGAL4^miRs}

pros^{miR.FOFO2.0.Act5C}

P{Act5C(FOFO2.0)pros^miRsGAL4^miRs}

w^*; P{Act5C(FOFO2.0)pros^miRsGAL4^miRs}attP40/CyO, P{Dfd-EYFP}2

y¹ v¹; P{TRiP.JF02308}attP2/TM3, Sb¹

y¹ v¹; P{TRiP.HMJ02107}attP40/CyO

pros^VSH330051

P{VSH330051}

P{VSH330051}attP40

lncRNA:cherub^RNAi.UAS

P{UAS-lncRNA:cherub.RNAi}

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

numb¹

amorphic allele - genetic evidence

PM hybrid dysgenesis

numb¹/CyO

numb⁰³²³⁵

P-element activity

P{PZ}numb⁰³²³⁵ cn¹/CyO; ry⁵⁰⁶

numb²

amorphic allele - genetic evidence

diepoxybutane

numb^S52F

loss of function allele

numb¹⁵

amorphic allele - genetic evidence

ethyl methanesulfonate

numb³

amorphic allele - genetic evidence

diepoxybutane

brat^chs

ethyl nitrosourea

brat^k06028

P-element activity

y^d2 w¹¹¹⁸ P{ey-FLP.N}2 P{5xglBS-lacZ.38-1}TPN1; P{lacW}brat^k06028 P{neoFRT}40A/CyO y⁺

brat¹

ethyl methanesulfonate

brat¹ rdo¹ hook¹ pr¹/CyO

brat¹¹

amorphic allele - molecular evidence

formaldehyde

brat¹¹; P{UAS-btau::GFP.T:Myc}2/CyO, P{en1}wg^en11; P{UASp-brat.H}3

brat¹⁴

ethyl methanesulfonate

brat¹⁸

ethyl methanesulfonate

CyO, Duox^Cy dpy^lv1 pr¹ cn² / Ddc²⁷ brat¹⁸ pr¹ or^49h

brat^2L-150-11

amorphic allele - molecular evidence

ethyl methanesulfonate

brat^2L-192-9

amorphic allele - molecular evidence

ethyl methanesulfonate

mira^KO

loss of function allele

CRISPR/Cas9

mira^L44

loss of function allele

ethyl methanesulfonate

w^*; P{neoFRT}82B mira^L44 e^*/TM6B, P{Dfd-EYFP}3, Sb¹ Tb¹ ca¹

mira^ZZ176

loss of function allele

ethyl methanesulfonate

l(3)mbt^E2

ethyl methanesulfonate

l(3)mbt^E2/TM6C, Sb¹ Tb¹

l(3)mbt^GM76

ethyl methanesulfonate

l(3)mbt^ts1

ethyl methanesulfonate

w^*; l(3)mbt^ts1/TM6B, Tb¹

pins^P120

amorphic allele - molecular evidence

Delta2-3 transposase

pins^P62

loss of function allele

Delta2-3 transposase

pins^P17

amorphic allele - molecular evidence

Delta2-3 transposase

pins^P89

loss of function allele

Delta2-3 transposase

pros¹³⁹

loss of function allele

P-element activity

pros^C43

amorphic allele - genetic evidence

Delta2-3 transposase

pros^V17

loss of function allele

Delta2-3 transposase

pros^m1

amorphic allele - genetic evidence

ethyl methanesulfonate

pros¹⁷

amorphic allele - genetic evidence

Delta2-3 transposase

w^*; pros¹⁷/TM6B, Tb¹

pros^m2

amorphic allele - genetic evidence

ethyl methanesulfonate

pros^JO1

amorphic allele - genetic evidence

Delta2-3 transposase

pros^m5

amorphic allele - genetic evidence

ethyl methanesulfonate

pros^JO13

amorphic allele - genetic evidence

Delta2-3 transposase

pros¹⁴

amorphic allele - genetic evidence

P-element activity

pros^m4

amorphic allele - genetic evidence

ethyl methanesulfonate

pros^K816

amorphic allele - genetic evidence

ethyl methanesulfonate

pros^Il3

loss of function allele

pros^C7

amorphic allele - genetic evidence

Delta2-3 transposase

pros^m3

amorphic allele - genetic evidence

ethyl methanesulfonate

pros^D135

amorphic allele - genetic evidence

ethyl methanesulfonate

lncRNA:cherub^DEL

amorphic allele - molecular evidence

CRISPR/Cas9

References (33)

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