Sci. Signal., 27 April 2010
Coordinated RecoveryThe transcriptional co-repressor protein KAP1 represses the expression of genes involved in cell cycle arrest and apoptosis. To perform this function, KAP1 must be modified by small ubiquitin-like modifying (SUMO) proteins. Under basal conditions, SUMOylated KAP1 associates with KRAB-type zinc finger proteins at the promoters of its target genes. Under conditions of genotoxic stress, KAP1 is phosphorylated at Ser824 by the kinase ataxia-telangiectasia mutated (ATM), which inhibits SUMOylation of KAP1, leading to derepression of its target genes. Little is known, however, about the mechanisms that restore KAP1 SUMOylation and function after genotoxic stress. Li et al. show that two isoforms of protein phosphatase 1 (PP1) play distinct roles in the dephosphorylation and SUMOylation of KAP1. Whereas PP1 interacted with KAP1 under normal conditions and led to the dephosphorylation of KAP1 at Ser824, PP1β interacted with KAP1 with different kinetics and under conditions of genotoxic stress, such as in response to the induction of DNA double-strand breaks. PP1β recruitment was required to mediate the SUMOylation of dephosphorylated KAP1, thereby counteracting the effects of ATM and leading to the repression of KAP1 target genes. Together, these data implicate PP1 in regulating SUMOylation in response to DNA damage and provide insight into the recovery mechanisms of cells after genotoxic stress.
Citation: X. Li, H. H. Lin, H. Chen, X. Xu, H.-M. Shih, D. K. Ann, SUMOylation of the Transcriptional Co-Repressor KAP1 Is Regulated by the Serine and Threonine Phosphatase PP1. Sci. Signal. 3, ra32 (2010).
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