Human Disease Model Report: cancer, epithelial, compromised apoptosis and cell-cycle checkpoint defects

General Information

Name

cancer, epithelial, compromised apoptosis and cell-cycle checkpoint defects

FlyBase ID

FBhh0001054

Disease Ontology Term

carcinoma

Parent Disease

OMIM

Overview

In a background of apoptosis-deficient cells in imaginal discs, X-irradiation results in tumorigenic phenotypes, including overgrowth of targeted cells within the disc and delamination of the epithelium (see FBhh0001040). The additional effects of reduced function of genes that contribute to cell-cycle checkpoints have been assessed. RNAi-mediated reduction of grp (orthologous to human CHEK1) or mei-41 (orthologous to human ATR) enhances the tumorigenic phenotypes; these two genes are involved in DNA-damage-induced cell cycle arrest in G2.

[updated Jun. 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, epithelial, compromised apoptosis and cell-cycle checkpoint defects

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

KEGG Disease Pathways: Pathways in Cancer

Disease synonyms

Related Diseases

Related human health report(s)

cancer, epithelial, compromised apoptosis

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\grp

Gene Snapshot

grapes (grp) encodes a protein that functions in a cell cycle checkpoint pathway that responds to DNA damage. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

CAMK

Comments on ortholog(s)

High-scoring ortholog of human CHEK1 (1 Drosophila to 1 human). Dmel\grp shares 44% identity and 59% similarity with the human gene.

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\mei-41

Gene Snapshot

meiotic 41 (mei-41) encodes a protein that, together with mus304, promotes DNA damage-dependent responses, including repair and cell cycle checkpoint signalling. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human ATR (1 Drosophila to 1 human). Dmel\mei-41 shares 26% identity and 44% similarity with the human gene.

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 (1)

BacA\p35

Summary of Physical Interactions (7 groups)

grp

protein-protein

Interacting group

Assay

References

grp

enzymatic study, autoradiography, molecular weight estimation by silver staining

(Ilves et al., 2012)

grp - Cdc45

enzymatic study, autoradiography, molecular weight estimation by silver staining

(Ilves et al., 2012)

grp - Jwa

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

RNA-protein

Interacting group

Assay

References

grp - Dcr-2

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Nadimpalli et al., 2022)

grp - wisp

anti bait coimmunoprecipitation, primer specific pcr

(Cui et al., 2013)

mei-41

protein-protein

Interacting group

Assay

References

mei-41 - nej

anti tag coimmunoprecipitation, anti tag western blot

(Smolik and Jones, 2007)

BacA\p35

protein-protein

Interacting group

Assay

References

BacA\p35 - Dredd

anti tag coimmunoprecipitation, anti tag western blot

(Guntermann and Foley, 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (16 alleles)

grp

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

grp^GD4189

model of cancer

CEA with BacA\p35^UAS.cHa

(Dekanty et al., 2015)

grp^KK108548

model of cancer

CEA with BacA\p35^UAS.cHa

(Dekanty et al., 2015)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

grp^JF02588

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{T12.Aβ42.UAS.Tag:SS(nec)}

(Taylor et al., 2022)

grp^NIG.17161R

ameliorates neurodegenerative disease

modeled by Hsap\ATXN1^82Q.UAS

(Barclay et al., 2014)

grp^GS22185

exacerbates neurodegenerative disease

modeled by Hsap\ATXN1^82Q.UAS

(Barclay et al., 2014)

mei-41

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

mei-41^unspecified

model of cancer

CEA with wts^x1

(Busygina et al., 2004)

mei-41^GD4258

model of cancer

CEA with BacA\p35^UAS.cHa

(Dekanty et al., 2015)

mei-41^KK101792

model of cancer

CEA with BacA\p35^UAS.cHa

(Dekanty et al., 2015)

model of ataxia telangiectasia

CEA with tefu^GD11950

(Park et al., 2015)

Modifiers Based on Experimental Evidence ( 4 )

Allele

Disease

Interaction

References

mei-41^29D

ameliorates Bloom syndrome

modeled by Blm^D2, Blm^N1

(Lafave et al., 2014)

mei-41^GL00284

ameliorates cancer

modeled by N^ICN.UAS

(Wang et al., 2021)

mei-41^GD4258

model of cancer

is ameliorated by bsk^K53R.UAS

(Dekanty et al., 2015)

mei-41^RNAi.UAS.cUa

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{T12.Aβ42.UAS.Tag:SS(nec)}

(Taylor et al., 2022)

BacA\p35

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

BacA\p35^UAS.cHa

model of cancer

CEA with okr^KK107487

(Dekanty et al., 2015)

CEA with grp^GD4189

(Dekanty et al., 2015)

CEA with grp^KK108548

(Dekanty et al., 2015)

CEA with mei-41^GD4258

(Dekanty et al., 2015)

CEA with mei-41^KK101792

(Dekanty et al., 2015)

CEA with hid^UAS.cUa

(Rudrapatna et al., 2013)

CEA

(Perez-Garijo et al., 2004)

CEA with Bub3^GD9924

(Muzzopappa et al., 2017)

CEA with rod^GD8768

(Muzzopappa et al., 2017)

CEA with mud^HMS01458

(Muzzopappa et al., 2017)

CEA with Ras85D^V12.UAS

(Khalili et al., 2023)

model of carcinoma

CEA with Vps25^Pb2931

(Thompson et al., 2005)

CEA with hep^Act.UAS

(Uhlirova and Bohmann, 2006)

Modifiers Based on Experimental Evidence ( 5 )

Allele

Disease

Interaction

References

BacA\p35^GMR.PH

ameliorates tauopathy

modeled by Hsap\MAPT^GMR.Ex.PJ

(Jackson et al., 2002)

ameliorates retinal disease

modeled by norpA^EE5

(Chinchore et al., 2012)

ameliorates cancer

modeled by Alk^UAS.cLa

(Wolfstetter et al., 2020)

ameliorates ataxia telangiectasia

modeled by tefu^RNAi.UAS

(Rimkus et al., 2008)

BacA\p35^UAS.cHa

exacerbates cancer

modeled by Bub3^GD9924

(Barrio et al., 2023)

exacerbates brain cancer

modeled by l(3)mbt^GD4370, l(3)mbt^ts1

(Climent-Cantó et al., 2022)

ameliorates Alzheimer's disease

modeled by Tom40^{UAS.Tag:FLAG,Tag:HA}

(Periasamy et al., 2022)

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.QUAS.Tag:SS(nec)}

(Sheng et al., 2023)

ameliorates tauopathy

modeled by Hsap\MAPT^{T231A.S235A.UAS}

(Steinhilb et al., 2007)

modeled by Hsap\MAPT^{S396A.S404A.UAS}

(Steinhilb et al., 2007)

modeled by Hsap\MAPT^{S202A.T205A.UAS}

(Steinhilb et al., 2007)

modeled by Hsap\MAPT^UAS.cWa

(Steinhilb et al., 2007)

ameliorates amyotrophic lateral sclerosis

modeled by Hsap\TARDBP^UAS.YFP.cEa

(Estes et al., 2011)

modeled by Hsap\TARDBP^{A315T.UAS.YFP}

(Estes et al., 2011)

ameliorates neurodegenerative disease

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

(Wong et al., 2008)

ameliorates microcephaly

modeled by mad2^G6595, Sas-4^s2214

(Poulton et al., 2017)

exacerbates carcinoma

modeled by scrib¹

(Zheng et al., 2023, Brumby and Richardson, 2003)

modeled by l(2)gl⁴

(Rusu et al., 2021)

ameliorates retinitis pigmentosa 4

modeled by ninaE^P37H

(Galy et al., 2005)

ameliorates human immunodeficiency virus infectious disease

modeled by HIV-1\Vpu^UAS.cLa

(Marchal et al., 2012)

ameliorates myotonia congenita

modeled by mst^JF03280

(Min et al., 2017)

ameliorates cancer

modeled by Ras85D^V12.UAS, scrib⁶⁷³

(Pérez et al., 2017)

BacA\p35^UAS.cUa

ameliorates gastrointestinal adenoma

modeled by Apc^Q8, Apc2^g10

(Suijkerbuijk et al., 2016)

ameliorates cytochrome-c oxidase deficiency disease

modeled by Scox^GD898

(Martínez-Morentin et al., 2015)

exacerbates cancer

modeled by Hsap\CDH3^UASp.cPa

(Faria et al., 2023)

ameliorates autosomal dominant cerebellar ataxia

modeled by Hsap\ATXN1^82.UAS

(Ghosh and Feany, 2004)

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

(Ghosh and Feany, 2004)

exacerbates carcinoma

modeled by Delta^UAS.cDa, lola^GS88A8

(Pérez et al., 2015)

ameliorates myotonic dystrophy type 2

modeled by Zzzz\CCTG^UAS.106

(Yenigun et al., 2017)

ameliorates severe acute respiratory syndrome

modeled by HCoV-SARS\3a^{UAS.CUHK-W1.EGFP}

(Wong et al., 2005)

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{3-42.E3Q.UAS.Tag:SS(rPENK)}

(Tsuda et al., 2017)

ameliorates cancer

modeled by Egfr^UAS.cBa, mir-8^UAS.cUa

(Eichenlaub et al., 2016)

ameliorates Coronavirus infectious disease

modeled by HCoV-SARS\M^{UAS.CUHK-Su10}

(Chan et al., 2007)

exacerbates Alexander disease

modeled by Hsap\GFAP^R79H.UAS

(Wang et al., 2022)

BacA\p35^lexAop.cEa

ameliorates juvenile polyposis syndrome

modeled by shn^KK101278

(Zhou et al., 2021)

BacA\p35^QUAS.cPGa

ameliorates Huntington's disease

modeled by Hsap\HTT^{Q25.ex1.UAS.GFP}, Hsap\HTT^{Q91.ex1.QUAS.mCherry}

(Donnelly et al., 2020)

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

BacA\p35^{UASp.Tag:FLAG}

P{UASp-p35.Flag}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

mei-41^GD4258

P{GD4258}

w¹¹¹⁸; P{GD4258}v11251

y¹ sc^* v¹ sev²¹; P{TRiP.GL00284}attP2

mei-41^HMS02331

P{TRiP.HMS02331}

y¹ v¹; P{TRiP.HMS02331}attP40/CyO

w¹¹¹⁸; P{GD4189}v12680/TM3

grp^JF02588

P{TRiP.JF02588}

y¹ v¹; P{TRiP.JF02588}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01573}attP2/TM3, Sb¹

y¹ sc^* v¹ sev²¹; P{TRiP.HMC05162}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

mei-41^unspecified

mei-41^29D

P-element activity

C(1)RM, y¹/w^* mei-41^29D f¹; P{GAL4::VP16-nanos.UTR}CG6325^MVD1

grp⁰⁶⁰³⁴

loss of function allele

P-element activity

P{PZ}grp⁰⁶⁰³⁴ cn¹/CyO; ry⁵⁰⁶

grp²

loss of function allele

P-element activity

grp⁰²²⁵⁷

loss of function allele

P-element activity

grp^fsA4

loss of function allele

P-element activity

grp²⁰⁹

loss of function allele

P-element activity

grp^Z5170

loss of function allele

ethyl methanesulfonate

grp^GS22185

References (3)

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