Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

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

RESEARCH ARTICLES

Editor's Summary

Coordinated Recovery
The 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{alpha} 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).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Phosphoproteomic analysis reveals that PP4 dephosphorylates KAP-1 impacting the DNA damage response.
D.-H. Lee, A. A. Goodarzi, G. O. Adelmant, Y. Pan, P. A. Jeggo, J. A. Marto, and D. Chowdhury (2012)
EMBO J. 31, 2403-2415
   Abstract »    Full Text »    PDF »
SUMO Binding by the Epstein-Barr Virus Protein Kinase BGLF4 Is Crucial for BGLF4 Function.
R. Li, L. Wang, G. Liao, C. M. Guzzo, M. J. Matunis, H. Zhu, and S. D. Hayward (2012)
J. Virol. 86, 5412-5421
   Abstract »    Full Text »    PDF »
KAP1 Protein: An Enigmatic Master Regulator of the Genome.
S. Iyengar and P. J. Farnham (2011)
J. Biol. Chem. 286, 26267-26276
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882