Human Disease Model Report: ovarian carcinoma, RAS-PKRC-related

General Information

Name

ovarian carcinoma, RAS-PKRC-related

FlyBase ID

FBhh0001585

Disease Ontology Term

ovarian carcinoma

Parent Disease

OMIM

Overview

In this ovarian carcinoma (OC) model, tumorigenesis is driven by expression of the Ras85D^V12 and aPKC^ΔN.UAS targeted to the follicle epithelium via GAL4-UAS and restricted to adulthood via a temperature-sensitive GAL4 repressor. Overproliferation, loss of cell polarity, and defective differentiation are observed; metastasis is not observed. OC-bearing flies show significantly accelerated mortality compared with controls; lethality appears to arise from systemic effects of the tumor on the host, termed paraneoplasias. One of the observed changes is overproduction of multiple secreted components of the clotting cascade that trigger hypercoagulation of the hemolymph, followed subsequently by hypocoagulation. Thus this system provides a model for investigation of mechanisms of and possible treatment of tumor-driven coagulopathy.

The constitutively active Ras85D mutation, Ras85D^V12, is analogous to one of the most common oncogenic mutations found in human RAS proteins. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G12V in the fly Ras85D gene (corresponds to G12V in the human KRAS, HRAS and NRAS genes).

[updated Jun. 2024 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: ovarian carcinoma, RAS-PKRC-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

The RAS proteins are members of a large superfamily of low-molecular-weight GTP-binding proteins. The RAS proteins control signalling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. Three members of the RAS family, HRAS, KRAS and NRAS, are found to be activated by mutation in human tumors. These three members are very closely related, having 85% amino acid sequence identity (Downward, 2003; pubmed:12509763).

(FlyBase Curators, 2013-)

The PKC family of serine/threonine kinases are involved in a variety of cellular processes such as proliferation, differentiation and secretion. The PKC family comprises at least eight members grouped by their activation mechanism. Unlike the classical PKC isoenzymes which are calcium-dependent, PRKCI and PRKCZ exhibit kinase activity that is independent of calcium and also independent of diacylglycerol. [Gene Cards, PRKCI and PRKCZ; 2024.06.19]

(FlyBase Curators, 2013-)

External links

Disease synonyms

Related Diseases

Related human health report(s)

cancer, epithelial, Par-complex-related

cancer, multiple, RAS-related

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\aPKC

Gene Snapshot

atypical protein kinase C (aPKC) encodes a member of the conserved Par complex and is asymmetrically localized to the apical cortex, where it phosphorylates and thus excludes the basal determinants encoded by mira and numb. It is involved in neuroblast proliferation and self-renewal. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human PRKCI and PRKCZ (1 Drosophila to 2 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\Ras85D

Gene Snapshot

Ras oncogene at 85D (Ras85D) encodes a protein that acts downstream of several cell signals, most notably from Receptor Tyrosine Kinases, to regulate tissue growth and development. When abnormally activated it can direct developmental defects and tissue hyperplasia, mimicking aspects of human disease including Rasopathies and cancer, respectively. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human genes KRAS, HRAS, and NRAS (many to many; multiple paralogs and orthologs in both species; for these three human genes, Ras85D is the highest-scoring ortholog in Drosophila.

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 (64 groups)

aPKC

RNA-protein

Interacting group

Assay

References

aPKC - kin17

anti tag coimmunoprecipitation, reverse transcription pcr

(Connell et al., 2024)

aPKC - orb

anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Barr et al., 2019)

aPKC - orb2

pull down, western blot, electrophoretic mobility shift assay, autoradiography, anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Xu et al., 2014, Mastushita-Sakai et al., 2010)

protein-protein

Interacting group

Assay

References

aPKC

enzymatic study, autoradiography

(Colosimo et al., 2010)

aPKC - aurA

enzymatic study, autoradiography

(Wirtz-Peitz et al., 2008)

aPKC - baz

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

(Holly et al., 2020, Casas-Tintó and Ferrús, 2019, Padash Barmchi et al., 2016, Goh et al., 2013, Duchi et al., 2010, Morais-de-Sá et al., 2010, Simões et al., 2010, Kim et al., 2009, Krahn et al., 2009, Wirtz-Peitz et al., 2008, Wang and Riechmann, 2007, Djiane et al., 2005, Harris and Peifer, 2005, Betschinger et al., 2003, Wodarz et al., 2000)

aPKC - Cdc42

anti bait coimmunoprecipitation, western blot

(Leibfried et al., 2013)

aPKC - clu

anti bait coimmunoprecipitation, western blot

(Goh et al., 2013)

aPKC - crb

pull down, anti tag western blot, western blot, phenotype-based detection assay, fluorescence microscopy, inferred by author

(Kempkens et al., 2006, Sotillos et al., 2004)

aPKC - Dap160

pull down, autoradiography, anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry

(Chabu and Doe, 2008)

aPKC - dlg1

enzymatic study, Identification by mass spectrometry

(Golub et al., 2017)

aPKC - futsch

anti bait coimmunoprecipitation, western blot

(Ruiz-Canada et al., 2004)

aPKC - fz

anti tag coimmunoprecipitation, western blot

(Djiane et al., 2005)

aPKC - kibra

anti tag coimmunoprecipitation, western blot

(Jin et al., 2015)

aPKC - l(2)gl

experimental knowledge based, anti bait coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, peptide massfingerprinting

(Portela et al., 2024, Calero-Cuenca et al., 2016, Goh et al., 2013, Guruharsha et al., 2011, Tian and Deng, 2008, Wirtz-Peitz et al., 2008, Betschinger et al., 2003)

aPKC - Magi

anti bait coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy

(Padash Barmchi et al., 2016)

aPKC - mira

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)

aPKC - mts

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

(Chabu and Doe, 2009, Ogawa et al., 2009)

aPKC - Myo10A

pull down, autoradiography, two hybrid

(Liu et al., 2008)

aPKC - nuf

pull down, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, protein kinase assay, autoradiography

(Calero-Cuenca et al., 2016)

aPKC - numb

pull down, western blot

(Wirtz-Peitz et al., 2008)

aPKC - par-1

anti tag coimmunoprecipitation, western blot, peptide massfingerprinting

(Calero-Cuenca et al., 2016, Tian and Deng, 2008)

aPKC - par-6

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, pull down, autoradiography, peptide massfingerprinting, two hybrid, anti tag western blot, experimental knowledge based

(Nunes de Almeida et al., 2019, Calero-Cuenca et al., 2016, Neumüller et al., 2012, Guruharsha et al., 2011, Atwood and Prehoda, 2009, Kim et al., 2009, Wirtz-Peitz et al., 2008, Djiane et al., 2005, Hutterer et al., 2004, Ruiz-Canada et al., 2004, Betschinger et al., 2003)

aPKC - Patj

pull down, western blot, anti tag western blot

(Sotillos et al., 2004)

aPKC - pbl

anti tag coimmunoprecipitation, western blot

(Rosa et al., 2015)

aPKC - pon

pull down, western blot

(Wirtz-Peitz et al., 2008)

aPKC - Rap1

anti tag coimmunoprecipitation, western blot

(Carmena et al., 2011)

aPKC - ref(2)P

anti bait coimmunoprecipitation, anti tag western blot

(Avila et al., 2002)

aPKC - sdt

anti bait coimmunoprecipitation, western blot

(Koch et al., 2016)

aPKC - sif

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

(Wang et al., 2018)

aPKC - Tsp2A

anti tag coimmunoprecipitation, anti tag western blot

(Xu et al., 2019)

aPKC - tws

anti bait coimmunoprecipitation, western blot

(Chabu and Doe, 2009)

aPKC - Vhl

anti tag coimmunoprecipitation, western blot

(Duchi et al., 2010)

aPKC - wupA

anti bait coimmunoprecipitation, western blot

(Casas-Tintó and Ferrús, 2019)

aPKC - yrt

anti bait coimmunoprecipitation, western blot, enzymatic study, autoradiography, peptide massfingerprinting, pull down

(Gamblin et al., 2014)

Ras85D

protein-protein

Interacting group

Assay

References

Ras85D - alt

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Arc1

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - ave

pull down, anti tag western blot

(Maisonneuve et al., 2024)

Ras85D - CG31550

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - cindr

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - cno

two hybrid, anti tag coimmunoprecipitation, autoradiography

(Boettner and Van Aelst, 2007, Carmena et al., 2006)

Ras85D - Droj2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - eIF3i

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - glo

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Gyc76C

anti tag coimmunoprecipitation, anti tag western blot

(Iwashita et al., 2020)

Ras85D - lark

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - mod(mdg4)

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Nf1

gtpase assay, autoradiography

(Walker et al., 2006)

Ras85D - Nop60B

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Pi3K92E

two hybrid, pull down, western blot

(Orme et al., 2006)

Ras85D - pico

two hybrid

(Lyulcheva et al., 2008)

Ras85D - Pyk

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Raf

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

(Yang and Terman, 2012, Ding et al., 2010, Mishra et al., 2005)

Ras85D - rau

pull down, anti tag western blot

(Sieglitz et al., 2013)

Ras85D - Rgl

two hybrid

(Mirey et al., 2003)

Ras85D - RpL6

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpL15

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpL21

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpL23A

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpL24

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpS2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpS27

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - spri

anti tag coimmunoprecipitation, anti tag western blot

(Jekely et al., 2005)

Ras85D - Sumo

anti tag coimmunoprecipitation, Identification by mass spectrometry, pull down, covalent binding, western blot

(Nie et al., 2009)

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

aPKC

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

aPKC^{UAS.Tag:CAAX(Unk)}

model of cancer

CEA with hep^UAS.cBa

(Bunker et al., 2015)

CEA with ph-p^GD4480

(Bunker et al., 2015)

model of high grade glioma

CEA

(Paglia et al., 2017)

aPKC^M.UAS

model of carcinoma

CEA

(Eder et al., 2005)

aPKC^ΔN.UAS

model of ovarian carcinoma

CEA with Ras85D^V12.UAS

(Hsi et al., 2023)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

aPKC^UAS.ORF

exacerbates cancer

modeled by Myc^UAS.cZa, p53^{RNAi.UAS.RasG12D}

(Diaz et al., 2024)

aPKC^{UAS.Tag:CAAX(Unk)}

model of high grade glioma

is ameliorated by Myc^RNAi.UAS.cUa

(Paglia et al., 2017)

is exacerbated by Pi3K92E^CAAX.UAS

(Paglia et al., 2017)

aPKC^ΔN.UAS

model of cancer

is NOT ameliorated by bsk^K53R.UAS

(Bunker et al., 2015)

Ras85D

Models Based on Experimental Evidence ( 17 )

Allele

Disease

Evidence

References

Ras85D^HMS01294

model of Noonan syndrome 3

CEA

(Cattaneo et al., 2020)

Ras85D^G12V.UAS

model of cancer

CEA with RhoGEF2^RE.UAS

(Khoo et al., 2013)

CEA with Rok^CAT.UAS

(Khoo et al., 2013)

CEA with sqh^{E20E21.UAS.cCa}

(Khoo et al., 2013)

Ras85D^G13Q.UAS

model of cancer

CEA

(Xu et al., 2023)

CEA with Pten^HMS00044, Rbf^HMS03004

(Parkhitko et al., 2021)

Ras85D^N17.UAS

model of Noonan syndrome 3

CEA

(Cattaneo et al., 2020)

Ras85D^Q13.UAS

model of cancer

CEA

(Tamamouna et al., 2021)

Ras85D^V12.GMR

model of cancer

CEA

(Okada et al., 2023)

Ras85D^V12.S35.UAS

model of cardiomyopathy

CEA

(Yu et al., 2013)

model of carcinoma

CEC

(Karim and Rubin, 1998)

Ras85D^V12.UAS

model of carcinoma

CEA

(Martínez-Abarca Millán and Martín-Bermudo, 2023, Ito and Igaki, 2021, Kong et al., 2021, Rackley et al., 2021, Soler Beatty et al., 2021, Wei et al., 2021, Wu et al., 2021, Murcia et al., 2019, Zoranovic et al., 2018, Pérez et al., 2015, Igaki et al., 2006)

CEA with dlg1^GD4689

(Santabárbara-Ruiz and Léopold, 2021)

CEA with scrib⁶⁷³

(Amcheslavsky et al., 2018, Pérez et al., 2015)

CEC

(Rosen et al., 2019, Karim and Rubin, 1998)

CEC with scrib¹

(Rosen et al., 2019)

CEA with l(2)gl⁴

(Ding et al., 2022, Singh et al., 2022, Ito and Igaki, 2021, Wu et al., 2021, Mishra-Gorur et al., 2019, Zhang et al., 2019, Srivastava et al., 2007, Igaki et al., 2006)

CEA with Lkb1^4A4-2

(Rackley et al., 2021)

CEA with scrib¹

(Kong et al., 2021, Mishra-Gorur et al., 2019, Srivastava et al., 2007, Igaki et al., 2006, Uhlirova and Bohmann, 2006)

CEA with dlg1¹⁴

(Ito and Igaki, 2021, Igaki et al., 2006)

CEA with shg^k03401

(Igaki et al., 2006)

CEA with msn³²⁰⁸

(Kong et al., 2021)

CEA with sna^UAS.cAa

(Wu et al., 2021)

CEA with scrib^KK101128

(Murcia et al., 2019)

CEA with scrib^HMJ21977

(Snigdha et al., 2021)

CEA with Csk^Q156Stop

(Hirabayashi and Cagan, 2015)

CEA with Csk^Q156Stop, InR^A1325D.UAS

(Hirabayashi and Cagan, 2015)

model of cancer

CEA with fmt¹

(Ma et al., 2017)

CEA with PpV^Δ1

(Ma et al., 2017)

CEA with l(2)gl⁴

(Guo et al., 2020, Ma et al., 2017, Ma et al., 2013, Pagliarini and Xu, 2003)

CEA with PpV^GD7532

(Ma et al., 2017)

CEA

(Khalili et al., 2023, Martínez-Abarca Millán et al., 2023, Enomoto et al., 2021, Santabárbara-Ruiz and Léopold, 2021, Tamamouna et al., 2021, Ma et al., 2020, Jung et al., 2019, Rives-Quinto et al., 2017, Chabu and Xu, 2014, Hirabayashi et al., 2013, Ma et al., 2013)

CEA with scrib⁶⁷³

(Katheder et al., 2017, Pérez et al., 2017)

CEA with scrib¹

(Kakemura and Igaki, 2024, Cong et al., 2021, Hodgson et al., 2021, Katheder et al., 2017, Figueroa-Clarevega and Bilder, 2015, Külshammer et al., 2015, Stickel and Su, 2014, Willoughby et al., 2013, Wu et al., 2010, Pagliarini and Xu, 2003)

CEA with dlg1^GD4689

(Katheder et al., 2017, Muzzopappa et al., 2017, Figueroa-Clarevega and Bilder, 2015, Willecke et al., 2011)

CEA with scrib^j7B3

(Waghmare et al., 2024, Pagliarini and Xu, 2003)

CEA with Src64B^UAS.cCa

(Enomoto et al., 2021)

CEA with dlg1¹⁴

(Kakemura and Igaki, 2024, Pagliarini and Xu, 2003)

CEA with baz⁴

(Pagliarini and Xu, 2003)

CEA with sdt^XN

(Pagliarini and Xu, 2003)

CEA with Cdc42¹

(Pagliarini and Xu, 2003)

CEA with dor^C107

(Chi et al., 2010)

CEA with dor⁸

(Chi et al., 2010)

CEA with dor^D185

(Chi et al., 2010)

CEA with car^RNAi.UAS

(Chi et al., 2010)

CEA with Vps16A^RNAi.UAS.WIZ

(Chi et al., 2010)

CEA with upd1^UAS.cUa

(Wu et al., 2010)

CEA with upd2^UAS.cUa

(Wu et al., 2010)

CEA with upd1^UAS.cUa, upd2^UAS.cUa, upd3^UAS.cUa

(Wu et al., 2010)

CEA with l(2)gl^unspecified

(Xu et al., 2023, Wu et al., 2010)

CEA with pnut^GD1512

(Gerlach et al., 2018)

CEC with l(2)gl⁴

(Ma et al., 2014)

CEA with Hsap\S100A4^wt.UAS

(Ismail et al., 2017)

CEA with scrib^RNAi.UAS.cUa

(Hodgson et al., 2021)

CEA with Csk^Q156Stop

(Hirabayashi et al., 2013)

CEA with scrib^KK101128

(Muzzopappa et al., 2017)

CEA with mud^JF02911

(Muzzopappa et al., 2017)

CEA with mud^HMS01458

(Muzzopappa et al., 2017)

CEA with N^RNAi.P.UAS

(Tamamouna et al., 2021)

CEA with N^DN.UAS.cUa

(Xu et al., 2023)

CEA with emei^GD3587

(Ma et al., 2020)

CEA with Rox8^GD11645

(Guo et al., 2020)

CEA with BacA\p35^UAS.cHa

(Khalili et al., 2023)

CEA with dlg1^RNAi.UAS.cUa

(Bakopoulos et al., 2023)

model of intestinal cancer

CEA

(Cabrera et al., 2023, Nászai et al., 2021)

CEA with Apc2^N175K, Apc^Q8

(Martorell et al., 2014, Martorell et al., 2014)

model of colorectal cancer

CEA

(Bangi et al., 2012)

model of leukemia

CEA

(Arefin et al., 2017)

CEA with l(2)gl^KK100777

(Arefin et al., 2017)

CEA with scrib^KK101128

(Arefin et al., 2017)

model of benign neoplasm

CEA with Alg9^c02021

(de Vreede et al., 2018)

DOES NOT model cancer

CEA with Hsap\S100A4^Δ2.UAS

(Ismail et al., 2017)

model of heart disease

CEA

(Karekar et al., 2021)

model of prostate cancer

CEA

(Rambur et al., 2020)

model of high grade glioma

CEA

(Kumar et al., 2024)

CEA with Pten^RNAi.UAS.cUa

(Cheng et al., 2016)

model of kidney cancer

CEA

(Zeng et al., 2010)

model of ovarian carcinoma

CEA with aPKC^ΔN.UAS

(Hsi et al., 2023)

model of hypertrophic cardiomyopathy

CEA

(Petersen et al., 2022)

Ras85D^V12.ey

model of carcinoma

CEC

(Karim and Rubin, 1998)

Ras85D^V12.cUa.UAS

model of cervical cancer

CEA

(Padash Barmchi et al., 2016)

CEA with Hsap\UBE3A^UAS.cRa, HPV18\E6^UAS.Tag:MYC

(Padash Barmchi et al., 2016)

CEA with Hsap\UBE3A^UAS.cRa, HPV18\E6^{V158A.UAS.Tag:MYC}

(Padash Barmchi et al., 2016)

model of cancer

CEA with l(2)gl⁴

(Fangninou et al., 2023, Liu et al., 2022, Yang et al., 2022)

CEA with Ptp61F^Δ

(Liu et al., 2022)

CEA with Syx7³¹¹⁹

(Liu et al., 2022)

CEA with Rabex-5³⁶⁷²

(Liu et al., 2022)

CEA with Vps36²⁵⁸⁶

(Liu et al., 2022)

CEA with TSG101^P26

(Liu et al., 2022)

CEA with N^DN.UAS.cUa

(Lee et al., 2021)

CEA with dlg1^RNAi.UAS.cUa

(Lodge et al., 2021)

CEA

(Yang et al., 2022, Dong et al., 2021, Yeom et al., 2021, Dunn et al., 2018, Vicente et al., 2018)

CEA with scrib¹

(Yang et al., 2022, Khezri et al., 2021)

CEA with baz⁴

(Yang et al., 2022)

CEA with fmt¹

(Yang et al., 2022)

CEA with dlg1^GD4689

(Yang et al., 2022)

CEA with Ptip³⁸⁰⁴

(Dong et al., 2021)

model of colorectal cancer

CEA

(Zipper et al., 2022)

CEA with Pten^sgRNA.UAS

(Zipper et al., 2022)

CEA with Med^sgRNA.UAS

(Zipper et al., 2022)

CEA with cic^sgRNA.UAS

(Zipper et al., 2022)

CEA with Apc2^sgRNA.UAS

(Zipper et al., 2022)

CEA with Apc^sgRNA.UAS

(Zipper et al., 2022)

CEA with p53^sgRNA.UAS

(Zipper et al., 2022)

CEA with p53^RNAi.UAS.cUa, Pten^GD13500, Apc^RNAi.UAS.cUa, Med^RNAi.UAS.cUa

(Bangi et al., 2016)

CEA with p53^RNAi.UAS.cUa, Pten^GD13500, Apc^RNAi.UAS.cUa

(Bangi et al., 2016)

CEA with p53^RNAi.UAS.cUa, Apc^RNAi.UAS.cUa, Med^RNAi.UAS.cUa

(Bangi et al., 2016)

CEA with Pten^GD13500, Apc^RNAi.UAS.cUa, Med^RNAi.UAS.cUa

(Bangi et al., 2016)

model of cardiomyopathy

CEA

(Yu et al., 2013)

model of adenocarcinoma

CEA with l(2)gl^GD4047

(Casas-Tintó et al., 2016)

CEA with l(2)gl^GD4047, wupA^JF02172

(Casas-Tintó et al., 2016)

model of carcinoma

CEA

(Guo et al., 2024, Hogan et al., 2009)

CEA with l(2)gl⁴

(Sun et al., 2019)

CEA with dlg1^HMS00172

(Toggweiler et al., 2016)

model of intestinal cancer

CEA with Apc^Q8

(Campbell et al., 2019)

CEA

(Kim et al., 2022, Dai et al., 2020, Singh et al., 2016)

CEA with Apc2^N175K, Apc^Q8

(Parisi et al., 2023)

CEA with Apc^GD1333, p53^GD4483

(Quintero and Bangi, 2023)

CEA with Apc^GD1333, Pten^RNAi.UAS.cUa, p53^GD4483

(Quintero and Bangi, 2023)

CEA with Apc^GD1333, Med^GD1483, p53^GD4483

(Quintero and Bangi, 2023)

model of high grade glioma

CEA with Pten^{RNAi.Exel.UAS}

(Gangwani et al., 2020)

CEA

(Liu et al., 2021)

model of brain cancer

CEA with dlg1^GD4689

(Manzanero-Ortiz et al., 2021)

CEA with l(2)gl^KK100777

(Manzanero-Ortiz et al., 2021)

CEA with wts^KK101055

(Manzanero-Ortiz et al., 2021)

CEA with scrib⁶⁷³

(Manzanero-Ortiz et al., 2021)

Ras85D^V152G.UASp

model of Noonan syndrome 3

CEA

(Cattaneo et al., 2020)

Ras85D^{G12V.UAS.Tag:FLAG,Tag:polyHis}

model of cancer

CEA

(Washington et al., 2020)

Ras85D^{Y4F.G12V.UAS.Tag:FLAG,Tag:polyHis}

model of cancer

CEA

(Washington et al., 2020)

Ras85D^V12.QUAS.cHa

model of cancer

CEA with scrib¹

(Hodgson et al., 2021)

Ras85D^V12.QUAS.cLa

model of cancer

CEA with scrib^{QUAS.HMS01490}

(Bakopoulos et al., 2023, Lodge et al., 2021)

Ras85D^G12D.UAS.cSa

model of pancreatic ductal adenocarcinoma

CEA with CycE^{UAS.Tag:HA.Medsh}, Med^{RNAi.UAS.CycE-HA}, p53^{RNAi.UAS.RasG12D}

(Sekiya et al., 2023)

Ras85D^{G12D.UAS.p53sh}

model of pancreatic ductal adenocarcinoma

CEA with CycE^{UAS.Tag:HA.Medsh}, Med^{RNAi.UAS.CycE-HA}, p53^{RNAi.UAS.RasG12D}

(Sekiya et al., 2023)

Modifiers Based on Experimental Evidence ( 19 )

Allele

Disease

Interaction

References

Ras85D^HMS01294

ameliorates hematologic cancer

modeled by mxc¹

(Kurihara et al., 2020)

Ras85D^ΔC40B

ameliorates multiple endocrine neoplasia type 2B

modeled by Ret^MEN2B.GMR

(Read et al., 2005)

Ras85D⁰⁶⁶⁷⁷

ameliorates autosomal dominant cerebellar ataxia

modeled by Hsap\ATXN1^82Q.UAS

(Park et al., 2013)

ameliorates multiple endocrine neoplasia type 2B

modeled by Ret^MEN2B.GMR

(Read et al., 2005)

ameliorates multiple endocrine neoplasia type 2A

modeled by Ret^MEN2A.GMR

(Read et al., 2005)

ameliorates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2006)

Ras85D^G13Q.UAS

model of cancer

is exacerbated by ITP^UAS.F

(Xu et al., 2023)

Ras85D^N17.UAS

ameliorates brain glioma

modeled by btl::Egfr^λ.UAS, Pi3K92E^{UAS.Tag:MYC,Tag:PM(hKRAS)}

(Read et al., 2009)

Ras85D^Q13.UAS

model of cancer

is ameliorated by Cat^UAS.cAa

(Tamamouna et al., 2021)

is ameliorated by Sod1^UAS.cAa

(Tamamouna et al., 2021)

is ameliorated by btl^DN.UAS

(Tamamouna et al., 2021)

Ras85D^V12.GMR

model of cancer

is ameliorated by InR^GL00139

(Okada et al., 2023)

is ameliorated by InR^JF01183

(Okada et al., 2023)

is ameliorated by InR^JF01482

(Okada et al., 2023)

is ameliorated by InR^K1409A.UAS

(Okada et al., 2023)

is ameliorated by NetB^Δ

(Okada et al., 2023)

is ameliorated by NetB^KK103672

(Okada et al., 2023)

is ameliorated by NetB^VSH330183

(Okada et al., 2023)

is ameliorated by unc-5^HMS01099

(Okada et al., 2023)

is ameliorated by unc-5^KK102074

(Okada et al., 2023)

is ameliorated by unc-5^MI04273

(Okada et al., 2023)

Ras85D^V12.UAS

model of carcinoma

is exacerbated by mys^RNAi.UAS.cUa

(Martínez-Abarca Millán and Martín-Bermudo, 2023)

is exacerbated by mys^RNAi.UAS.cUa

(Martínez-Abarca Millán and Martín-Bermudo, 2023)

is ameliorated by Atg1^GD7149

(Pérez et al., 2015)

is ameliorated by HAdV-C\E4orf4^UAS.cPa

(Rosen et al., 2019)

is ameliorated by HAdV-C\E4orf4^UAS.cPb

(Rosen et al., 2019)

is exacerbated by dap^HMS01610

(Ito and Igaki, 2021)

is exacerbated by dap^HMS05362

(Ito and Igaki, 2021)

is ameliorated by pnt^P1.UAS

(Ito and Igaki, 2021)

is exacerbated by hep^Act.UAS

(Uhlirova and Bohmann, 2006)

is exacerbated by egr^UAS.cIa

(Igaki et al., 2006)

is exacerbated by ZnT86D^KK101698

(Wei et al., 2021)

is exacerbated by msn¹⁷²

(Kong et al., 2021)

is exacerbated by msn³²⁰⁸

(Kong et al., 2021)

is exacerbated by l(2)gl⁴

(Wu et al., 2021)

is exacerbated by sna^UAS.cAa

(Wu et al., 2021)

is ameliorated by rl^GD4697

(Murcia et al., 2019)

is exacerbated by Tsp29Fb^GD1018

(Zoranovic et al., 2018)

is ameliorated by Tsp29Fb^UAS.Tag:HA

(Zoranovic et al., 2018)

is ameliorated by Raf^DN.UAS

(Zoranovic et al., 2018)

is ameliorated by Hsap\CDKN1A^UAS.cHa

(Karim and Rubin, 1998)

is ameliorated by Raf^XS-2541

(Karim and Rubin, 1998)

is exacerbated by rl^Sem

(Karim and Rubin, 1998)

is exacerbated by Egfrap^ΔSH2

(Soler Beatty et al., 2021)

is exacerbated by Egfrap^HMJ23378

(Soler Beatty et al., 2021)

is exacerbated by Egfrap^LS

(Soler Beatty et al., 2021)

is exacerbated by Egfrap^L

(Soler Beatty et al., 2021)

is exacerbated by PVRAP^HMJ23233

(Soler Beatty et al., 2021)

model of cancer

is ameliorated by Sec15^KK101708

(Chabu and Xu, 2014)

is ameliorated by Sec6^GD11616

(Chabu and Xu, 2014)

is ameliorated by Sec8^KK101531

(Chabu and Xu, 2014)

is ameliorated by Sec15¹

(Chabu and Xu, 2014)

is ameliorated by Sec15^GD12109

(Chabu and Xu, 2014)

is ameliorated by Src64B^GD12263

(Ma et al., 2013)

is ameliorated by Dronc^NIG.8091R

(Waghmare et al., 2024)

is ameliorated by bsk^DN.UAS

(Waghmare et al., 2024)

is ameliorated by sgg^S9A.UAS

(Waghmare et al., 2024)

is ameliorated by yki^RNAi.C.UAS

(Waghmare et al., 2024)

is ameliorated by yki^RNAi.N.UAS

(Waghmare et al., 2024)

is ameliorated by chinmo¹

(Enomoto et al., 2021)

is exacerbated by PVRAP¹

(Martínez-Abarca Millán et al., 2023)

is exacerbated by PVRAP^HMJ23233

(Martínez-Abarca Millán et al., 2023)

is exacerbated by by^33c

(Martínez-Abarca Millán et al., 2023)

is exacerbated by by^VSH330366

(Martínez-Abarca Millán et al., 2023)

is exacerbated by Csk^Q156Stop

(Hirabayashi et al., 2013)

is exacerbated by emei¹

(Ma et al., 2020)

is exacerbated by emei²

(Ma et al., 2020)

is exacerbated by emei³

(Ma et al., 2020)

is ameliorated by Arc1^esm18

(Khalili et al., 2023)

is exacerbated by Nek2^UAS.GFP

(Das et al., 2013)

model of intestinal cancer

is ameliorated by shg^HMS00693

(Cabrera et al., 2023)

is ameliorated by shg^JF02769

(Cabrera et al., 2023)

is ameliorated by Cortactin^HMS00658

(Cabrera et al., 2023)

is ameliorated by Cortactin^KK108594

(Cabrera et al., 2023)

exacerbates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2006)

exacerbates gastrointestinal system cancer

modeled by Apc2^g10, Apc^Q8

(Wang et al., 2013)

model of colorectal cancer

is ameliorated by Jra^NIG.2275R

(Bangi et al., 2012)

is ameliorated by bsk^DN.UAS

(Bangi et al., 2012)

is ameliorated by bsk^HMS00777

(Bangi et al., 2012)

is exacerbated by hep^Act.UAS

(Bangi et al., 2012)

is exacerbated by imd^UAS.cGa

(Bangi et al., 2012)

is ameliorated by Timp^UAS.cPa

(Bangi et al., 2012)

ameliorates cancer

modeled by dlg1^A40.2

(Parisi et al., 2014)

exacerbates carcinoma

modeled by scrib¹

(Brumby and Richardson, 2003)

modeled by arm^UAS.Exel

(Zhang et al., 2019)

model of prostate cancer

is ameliorated by Egfr^GD1654

(Rambur et al., 2020)

is ameliorated by Pi3K92E^HMC05152

(Rambur et al., 2020)

is ameliorated by mTor^GL00156

(Rambur et al., 2020)

is ameliorated by rl^HMS00173

(Rambur et al., 2020)

is ameliorated by spi^HMS01120

(Rambur et al., 2020)

exacerbates intestinal cancer

modeled by Rab11^KK108297

(Nie et al., 2019)

exacerbates cancer

modeled by Hipk^UAS.Tag:HA

(Blaquiere et al., 2018)

model of kidney cancer

is ameliorated by Pka-C1^B3

(Zeng et al., 2010)

is ameliorated by mTor^ΔP

(Zeng et al., 2010)

exacerbates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.UAS.cUa}

(Cheng et al., 2021)

exacerbates hematologic cancer

modeled by mxc¹

(Kurihara et al., 2020)

Ras85D^V12.ey

model of carcinoma

is ameliorated by Raf^XS-2541

(Karim and Rubin, 1998)

Ras85D^e1B

ameliorates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2006)

exacerbates viral infectious disease

modeled by EBV\BZLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates infectious mononucleosis

modeled by EBV\BZLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates Epstein-Barr virus hepatitis

modeled by EBV\BZLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

ameliorates gastrointestinal system cancer

modeled by Apc2^g10, Apc^Q8

(Wang et al., 2013)

exacerbates tuberous sclerosis

modeled by Tsc1^UAS.cTa, gig^UAS.cTa

(Tapon et al., 2001)

ameliorates cancer

modeled by Alk^UAS.cLa

(Wolfstetter et al., 2020)

Ras85D^e2F

ameliorates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2006)

Ras85D^unspecified

ameliorates neurofibromatosis

modeled by Nf1^E2

(Walker et al., 2006)

Ras85D^V12.cUa.UAS

model of cancer

is exacerbated by Ptp61F^Δ

(Liu et al., 2022)

is exacerbated by ex^e1

(Liu et al., 2022)

is exacerbated by Not3^KK102144

(Vicente et al., 2018)

is exacerbated by M6^W186stop

(Dunn et al., 2018)

is ameliorated by Ptip³⁸⁰⁴

(Dong et al., 2021)

is exacerbated by p53^UAS.cUa

(Dong et al., 2021)

is ameliorated by Ilp8^MI00727

(Yeom et al., 2021)

model of intestinal cancer

is ameliorated by Cortactin^HMS00658

(Kim et al., 2022)

is exacerbated by Clbn^1Q

(Dai et al., 2020)

model of high grade glioma

is ameliorated by Nmnat^RNAi.UAS.cUa

(Liu et al., 2021)

is ameliorated by Dcp-1^RNAi.UAS.cUa

(Liu et al., 2021)

is exacerbated by Nmnat^UAS.PC

(Liu et al., 2021)

exacerbates carcinoma

modeled by Nkap^GD11807

(Guo et al., 2024)

model of carcinoma

is exacerbated by Nkap^GD11807

(Guo et al., 2024)

Ras85D^GD12553

ameliorates colorectal cancer

modeled by Src42A^CA.UAS

(Cordero et al., 2014)

modeled by Src64B^UAS.cCa

(Cordero et al., 2014)

ameliorates neurofibromatosis

modeled by Nf1^JF01866

(Georganta et al., 2021)

Ras85D^KK108029

ameliorates colorectal cancer

modeled by Src42A^CA.UAS

(Cordero et al., 2014)

modeled by Src64B^UAS.cCa

(Cordero et al., 2014)

ameliorates intestinal cancer

modeled by Egfr^UAS.cBa

(Nászai et al., 2021)

Ras85D^JF02478

ameliorates colorectal cancer

modeled by SH3PX1^HMJ21552

(Zhang et al., 2019)

Ras85D^{G12V.UAS.Tag:FLAG,Tag:polyHis}

model of cancer

is exacerbated by Egfr^2.UAS

(Washington et al., 2020)

is ameliorated by Rabex-5^{DPYT.UAS.Tag:MYC}

(Washington et al., 2020)

is exacerbated by hop^JF01267

(Washington et al., 2020)

Ras85D^{Y4F.G12V.UAS.Tag:FLAG,Tag:polyHis}

model of cancer

is exacerbated by Egfr^2.UAS

(Washington et al., 2020)

is ameliorated by Rabex-5^{DPYT.UAS.Tag:MYC}

(Washington et al., 2020)

Ras85D^DN.UAS.cUa

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.UAS.cUa}

(Cheng 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

Ras85D^V152G.UASp

P{UASp-Ras85D.V152G}

Ras85D^{G12V.UAS.Tag:FLAG,Tag:polyHis}

P{UAS-FH-Ras85D.G12V}

Ras85D^{Y4F.G12V.UAS.Tag:FLAG,Tag:polyHis}

P{UAS-FH-Ras85D.Y4F.G12V}

Ras85D^V12.QUAS.cHa

P{QUAS-Ras85D.V12.H}

Ras85D^V12.QUAS.cLa

PBac{QUAS-Ras85D.V12.L}

Ras85D^{G12D.UAS.p53sh}

P{UAS-Ras85D(G12D).UAS-p53(shRNA)}

Ras85D^V12.UAS

P{UAS-Ras85D.V12}

w¹¹¹⁸; P{UAS-Ras85D.V12}TL1

Ras85D^N17.UAS

P{UAS-Ras85D.N17}

P{UAS-Ras85D.N17}TL1, w¹¹¹⁸

P{UAS-Ras85D.V12.S35}

aPKC^{UAS.Tag:CAAX(Unk)}

P{UAS-aPKC.WT.CAAX}

aPKC^UAS.ORF

M{UAS-aPKC.ORF}

M{UAS-aPKC.ORF}ZH-86Fb

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Ras85D^{TH201501177.S}

w¹¹¹⁸; P{GD12553}v28129

y¹ v¹; P{TRiP.JF02478}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01294}attP2

Ras85D^GL00336

P{TRiP.GL00336}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00336}attP2/TM3, Sb¹

w¹¹¹⁸; P{GD1366}v2907/CyO

y¹ v¹; P{TRiP.JF01966}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01320}attP2

aPKC^GL00007

P{TRiP.GL00007}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00007}attP2

aPKC^HMS01411

P{TRiP.HMS01411}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01411}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01689}attP40

aPKC^HMC06305

P{TRiP.HMC06305}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC06305}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Ras85D⁰⁶⁶⁷⁷

P-element activity

P{PZ}Ras85D⁰⁶⁶⁷⁷ ry⁵⁰⁶/TM3, ry^RK Sb¹ Ser¹

Ras85D^e2F

sev¹⁴; Ras85D^e2F/TM3, Sb¹

Ras85D^e1B

ethyl methanesulfonate

sev¹⁴; Ras85D^e1B/TM3, Sb¹

Ras85D^unspecified

Ras85D^ΔC40B

loss of function allele

Ras85D^x7b

loss of function allele

P-element activity

Ras85D^Δ17b

amorphic allele - genetic evidence

aPKC^HC

amorphic allele - molecular evidence

CRISPR/Cas9

aPKC^k06403

loss of function allele

P-element activity

y^d2 w¹¹¹⁸ P{ey-FLP.N}2 P{5xglBS-lacZ.38-1}TPN1; P{neoFRT}42D P{lacW}aPKC^k06403 /CyO y⁺

References (5)

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