title: Identification of a novel, widespread, and functionally important PCNA-binding motif.
abstract: 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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Gilljam
authors.forename: Emadoldin
authors.initials: E
authors.lastname: Feyzi
authors.forename: Per A
authors.initials: PA
authors.lastname: Aas
authors.forename: Mirta M L
authors.initials: MM
authors.lastname: Sousa
authors.forename: Rebekka
authors.initials: R
authors.lastname: Müller
authors.forename: Cathrine B
authors.initials: CB
authors.lastname: Vågbø
authors.forename: Tara C
authors.initials: TC
authors.lastname: Catterall
authors.forename: Nina B
authors.initials: NB
authors.lastname: Liabakk
authors.forename: Geir
authors.initials: G
authors.lastname: Slupphaug
authors.forename: Finn
authors.initials: F
authors.lastname: Drabløs
authors.forename: Hans E
authors.initials: HE
authors.lastname: Krokan
authors.forename: Marit
authors.initials: M
authors.lastname: Otterlei
mesh_terms: D000071499:AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; D020816:Amino Acid Motifs / Q000235:genetics*; D000818:Animals; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D019473:Transcription Factors, TFII / Q000235:genetics / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D011993:Recombinant Fusion Proteins; D019473:Transcription Factors, TFII; D049308:Dioxygenases; C486440:ALKBH2 protein, human; D000071499:AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; D004250:DNA Topoisomerases, Type II; D045643:DNA Repair Enzymes