title: Nuclear translocation of p21(WAF1/CIP1) protein prior to its cytosolic degradation by UV enhances DNA repair and survival.
abstract: We previously reported that UV induced rapid proteasomal degradation of p21 protein in an ubiquitination-independent manner. Here, UV-induced p21 proteolysis was found to occur in the cytosol. Before cytosolic degradation, however, p21 protein translocated to and transiently accumulated in the nucleus. Nuclear translocation of p21 was not required for its degradation, but rather promoted DNA repair and cell survival. Overexpression of the wild type p21, but not the one with defective nuclear localization signal (NLS), reduced UV-induced DNA damage and cell death. Some of p21 protein translocated to the nucleus were associated with chromatin-bound PCNA and saved from UV-induced proteolysis. These data together show that p21 translocates to the nucleus to participate in DNA repair, while the rest is rapidly degraded in the cytosol. We propose that our findings reflect a mechanism to facilitate removal of damaged cells, enhancing DNA repair at the same time.
authors.affiliation: Department of Biochemistry, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hee Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jeongwon
authors.initials: J
authors.lastname: Sohn
mesh_terms: D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D002467:Cell Nucleus; D002470:Cell Survival; D002843:Chromatin / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism* / Q000528:radiation effects*; D003600:Cytosol / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: C493956:CDKN1A protein, human; D002843:Chromatin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D046988:Proteasome Endopeptidase Complex