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  • Title: Proliferating cell nuclear antigen destabilizes c-Abl tyrosine kinase and regulates cell apoptosis in response to DNA damage.
    Author: He X, Wei C, Song T, Yuan J, Zhang Y, Ma Q, Shi W, Zhong H.
    Journal: Apoptosis; 2009 Mar; 14(3):268-75. PubMed ID: 19156526.
    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.
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