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SUMOylation of hnRNP‐K is required for p53‐mediated cell‐cycle arrest in response to DNA damage
Author(s) -
Lee Seong Won,
Lee Moon Hee,
Park Jong Ho,
Kang Sung Hwan,
Yoo Hee Min,
Ka Seung Hyun,
Oh Young Mi,
Jeon Young Joo,
Chung Chin Ha
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.293
Subject(s) - biological sciences , library science , chinese academy of sciences , natural science , political science , biology , microbiology and biotechnology , philosophy , epistemology , china , computer science , law
Heterogeneous ribonucleoprotein‐K (hnRNP‐K) is normally ubiquitinated by HDM2 for proteasome‐mediated degradation. Under DNA‐damage conditions, hnRNP‐K is transiently stabilized and serves as a transcriptional co‐activator of p53 for cell‐cycle arrest. However, how the stability and function of hnRNP‐K is regulated remained unknown. Here, we demonstrated that UV‐induced SUMOylation of hnRNP‐K prevents its ubiquitination for stabilization. Using SUMOylation‐defective mutant and purified SUMOylated hnRNP‐K, SUMOylation was shown to reduce hnRNP‐K's affinity to HDM2 with an increase in that to p53 for p21‐mediated cell‐cycle arrest. PIAS3 served as a small ubiquitin‐related modifier (SUMO) E3 ligase for hnRNP‐K in an ATR‐dependent manner. During later periods after UV exposure, however, SENP2 removed SUMO from hnRNP‐K for its destabilization and in turn for release from cell‐cycle arrest. Consistent with the rise‐and‐fall of both SUMOylation and stability of hnRNP‐K, its ability to interact with PIAS3 was inversely correlated to that with SENP2 during the time course after UV exposure. These findings indicate that SUMO modification plays a crucial role in the control of hnRNP‐K's function as a p53 co‐activator in response to DNA damage by UV.