title: Proliferating cell nuclear antigen destabilizes c-Abl tyrosine kinase and regulates cell apoptosis in response to DNA damage.
abstract: The tyrosine kinase, c-Abl, plays important roles in many aspects of cellular function. The activity of c-Abl is tightly controlled, but the underlying mechanism is unclear. Recent studies suggest that c-Abl function is regulated by distinct lipids in different cell types. In the present study, we show that the DNA replication factor, proliferating cell nuclear antigen (PCNA), interacts with c-Abl and destabilizes c-Abl by promoting its polyubiquitination and degradation. Moreover, deletion of a domain in c-Abl, the PIP box, disrupts its interaction with PCNA, abolishes the PCNA-induced degradation of nuclear c-Abl, and substantially increases the nuclear c-Abl apoptotic function. These findings indicate that PCNA negatively regulates the stability of c-Abl and thereby inhibits apoptosis in the response to DNA damage.
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: He
authors.forename: Congwen
authors.initials: C
authors.lastname: Wei
authors.forename: Ting
authors.initials: T
authors.lastname: Song
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000502:physiology*; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D025801:Ubiquitin; D016315:Proto-Oncogene Proteins c-abl