Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-718
Gingras, A C; Caballero, M; Zarske, M; Sanchez, Amy; Hazbun, T R; Fields, S; Sonenberg, N; Hafen, E; Raught, B; Aebersold, R (2005). A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity. Molecular & Cellular Proteomics, 4(11):1725-1740.
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Using a combination of tandem affinity purification tagging and mass spectrometry, we characterized a novel, evolutionarily conserved protein phosphatase 4 (PP4)-containing complex (PP4cs, protein phosphatase 4, cisplatin-sensitive complex) that plays a critical role in the eukaryotic DNA damage response. PP4cs is comprised of the catalytic subunit PP4C; a known regulatory subunit, PP4R2; and a novel protein that we termed PP4R3. The Saccharomyces cerevisiae PP4R3 ortholog Psy2 was identified previously in a screen for sensitivity to the DNA-damaging agent and anticancer drug cisplatin. We demonstrated that deletion of any of the PP4cs complex orthologs in S. cerevisiae elicited cisplatin hypersensitivity. Furthermore human PP4R3 complemented the yeast psy2 deletion, and Drosophila melanogaster lacking functional PP4R3 (flfl) exhibited cisplatin hypersensitivity, suggesting a highly conserved role for PP4cs in DNA damage repair. Finally we found that PP4R3 may target PP4cs to the DNA damage repair machinery at least in part via an interaction with Rad53 (CHK2).
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|Item Type:||Journal Article, refereed|
|Communities & Collections:||07 Faculty of Science > Institute of Zoology (former)|
|Dewey Decimal Classification:||570 Life sciences; biology
590 Animals (Zoology)
|Date:||1 November 2005|
|Deposited On:||11 Feb 2008 12:17|
|Last Modified:||05 Apr 2016 12:15|
|Publisher:||American Society for Biochemistry and Molecular Biology|
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