Identification of a novel, widespread, and functionally important PCNA-binding motif

被引:146
作者
Gilljam, Karin M. [1 ]
Feyzi, Emadoldin [1 ]
Aas, Per A. [1 ]
Sousa, Mirta M. L. [1 ]
Mueller, Rebekka [1 ]
Vagbo, Cathrine B. [1 ]
Catterall, Tara C. [1 ]
Liabakk, Nina B. [1 ]
Slupphaug, Geir [1 ]
Drablos, Finn [1 ]
Krokan, Hans E. [1 ]
Otterlei, Marit [1 ]
机构
[1] Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway
关键词
TOPOISOMERASE-II-ALPHA; DNA-REPLICATION; PROTEIN INTERACTIONS; ALKYLATION DAMAGE; CANCER-THERAPY; REPAIR; SITES; RNA; INVOLVEMENT; DYNAMICS;
D O I
10.1083/jcb.200903138
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Numerous proteins, many essential for the DNA replication machinery, interact with proliferating cell nuclear antigen (PCNA) through the PCNA-interacting peptide (PIP) sequence called the PIP box. We have previously shown that the oxidative demethylase human AlkB homologue 2 (hABH2) colocalizes with PCNA in replication foci. In this study, we show that hABH2 interacts with a posttranslationally modified PCNA via a novel PCNA-interacting motif, which we term AlkB homologue 2 PCNA-interacting motif (APIM). We identify APIM in >200 other proteins involved in DNA maintenance, transcription, and cell cycle regulation, and verify a functional APIM in five of these. Expression of an APIM peptide increases the cellular sensitivity to several cytostatic agents not accounted for by perturbing only the hABH2-PCNA interaction. Thus, APIM is likely to mediate PCNA binding in many proteins involved in DNA repair and cell cycle control during genotoxic stress.
引用
收藏
页码:645 / 654
页数:10
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