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Sci. Signal., 27 April 2010
Vol. 3, Issue 119, p. ra32
[DOI: 10.1126/scisignal.2000781]

RESEARCH ARTICLES

SUMOylation of the Transcriptional Co-Repressor KAP1 Is Regulated by the Serine and Threonine Phosphatase PP1

Xu Li1,2, H. Helen Lin1, Hanqing Chen3, Xingzhi Xu3, Hsiu-Ming Shih4, and David K. Ann1,2*

1 Department of Molecular Pharmacology, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.
2 Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
3 College of Life Science, Capital Normal University, Beijing 100048, China.
4 Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, Republic of China.

Abstract: Krüppel-associated box (KRAB) domain–associated protein 1 [KAP1, also known as transcription intermediary factor–1β (TIF1β)] is a ubiquitous transcriptional co-repressor that is susceptible to phosphorylation at Ser824 by ataxia-telangiectasia mutated (ATM) and to modification by small ubiquitin-like modifying (SUMO) proteins. Here, we found that, whereas the protein phosphatase 1{alpha} isoform (PP1{alpha}) directly interacted with KAP1 under basal conditions, PP1β interacted with KAP1 only in response to genotoxic stress. Changes in the abundance of PP1{alpha} or PP1β had differential effects on the phosphorylation and SUMOylation states of KAP1 under basal conditions and in response to DNA double-strand breaks (DSBs). Chromatin immunoprecipitation and re-immunoprecipitation experiments revealed that PP1{alpha} and PP1β were recruited to KAP1 with different kinetics before and after the induction of DNA DSBs, which provided a mechanistic basis for the switch in the phosphorylation and SUMOylation states of KAP1. PP1β-dependent SUMOylation of KAP1 occurred by mechanisms that were dependent and independent of the phosphorylation status of Ser824. We posit a mechanism whereby the combined actions of PP1{alpha} and PP1β cause dephosphorylation of KAP1 at Ser824 and assure its SUMOylation to counter the effect of ATM, thereby regulating the transcription of KAP1 target genes in unstressed and stressed cells.

* To whom correspondence should be addressed. E-mail: dann{at}coh.org

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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