title: Interaction of proliferation cell nuclear antigen (PCNA) with c-Abl in cell proliferation and response to DNA damages in breast cancer.
abstract: Cell proliferation in primary and metastatic tumors is a fundamental characteristic of advanced breast cancer. Further understanding of the mechanism underlying enhanced cell growth will be important in identifying novel prognostic markers and therapeutic targets. Here we demonstrated that tyrosine phosphorylation of the proliferating cell nuclear antigen (PCNA) is a critical event in growth regulation of breast cancer cells. We found that phosphorylation of PCNA at tyrosine 211 (Y211) enhanced its association with the non-receptor tyrosine kinase c-Abl. We further demonstrated that c-Abl facilitates chromatin association of PCNA and is required for nuclear foci formation of PCNA in cells stressed by DNA damage as well as in unperturbed cells. Targeting Y211 phosphorylation of PCNA with a cell-permeable peptide inhibited the phosphorylation and reduced the PCNA-Abl interaction. These results show that PCNA signal transduction has an important impact on the growth regulation of breast cancer cells.
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Huajun
authors.initials: H
authors.lastname: Zhao
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Ho
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Lo
authors.forename: Alexsandra
authors.initials: A
authors.lastname: Espejo
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bedford
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Wang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*
chemical_list: D002843:Chromatin; D010446:Peptide Fragments; D018809:Proliferating Cell Nuclear Antigen; D016315:Proto-Oncogene Proteins c-abl