Reference Report

Reference
Citation	Malzer, E., Daly, M.L., Moloney, A., Sendall, T.J., Thomas, S.E., Ryder, E., Ryoo, H.D., Crowther, D.C., Lomas, D.A., Marciniak, S.J. (2010). Impaired tissue growth is mediated by checkpoint kinase 1 (CHK1) in the integrated stress response. J. Cell Sci. 123(17): 2892--2900. (Export to RIS)
FlyBase ID	FBrf0211608
Publication Type	Research paper
PubMed ID	20682638
PubMed Abstract	The integrated stress response (ISR) protects cells from numerous forms of stress and is involved in the growth of solid tumours; however, it is unclear how the ISR acts on cellular proliferation. We have developed a model of ISR signalling with which to study its effects on tissue growth. Overexpression of the ISR kinase PERK resulted in a striking atrophic eye phenotype in Drosophila melanogaster that could be rescued by co-expressing the eIF2alpha phosphatase GADD34. A genetic screen of 3000 transposon insertions identified grapes, the gene that encodes the Drosophila orthologue of checkpoint kinase 1 (CHK1). Knockdown of grapes by RNAi rescued eye development despite ongoing PERK activation. In mammalian cells, CHK1 was activated by agents that induce ER stress, which resulted in a G2 cell cycle delay. PERK was both necessary and sufficient for CHK1 activation. These findings indicate that non-genotoxic misfolded protein stress accesses DNA-damage-induced cell cycle checkpoints to couple the ISR to cell cycle arrest.
DOI	10.1242/jcs.070078
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Language of Publication	English
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Publication Type	Journal
Abbreviation	J. Cell Sci.
Title	Journal of Cell Science
Publication Year	1966-
ISBN/ISSN	0021-9533
Data from Reference
Alleles (17)
	BacA\p35^Scer\UAS.cUa CycD^Scer\UAS.cMa CycE^Scer\UAS.cLa grp²⁰⁹ grp⁰⁶⁰³⁴ grp^GD4189 grp^GS.M Hsap\MAPT^{R406W.Scer\UAS} Hsap\MAPT^Scer\UAS.cWa Mmus\Ppp1r15a^Scer\UAS.cMa Nc^pro.Scer\UAS PEK^KR.Scer\UAS PEK^Scer\UAS.cMa Scer\GAL4^GMR.PF Scer\GAL4^αTub84B.PL Scer\GAL80^ts.αTub84B th^Scer\UAS.cHa
Constructs (15)
	P{GAL4-ninaE.GMR} P{GD4189} P{GS-un} P{tubP-GAL4} P{tubP-GAL80^ts} P{UAS-CycD.M} P{UAS-CycE.L} P{UAS-DIAP1.H} P{UAS-GADD34.M} P{UAS-Hsap\MAPT.R406W} P{UAS-Hsap\MAPT.W} P{UAS-p35.U} P{UAS-PEK.KR} P{UAS-PEK.M} P{UAS-pro-dronc}
Genes (11)
	BacA\p35 CycD CycE grp Hsap\MAPT Mmus\Ppp1r15a Nc PEK Scer\GAL4 Scer\GAL80 th
Insertions (1)
	P{GS-un}grp^GS.M
Natural transposons (1)
	P-element