SUMOylation of pontin chromatin-remodeling complex reveals a signal integration code in prostate cancer cells

doi:10.1073/pnas.0710343105

SUMOylation of pontin chromatin-remodeling complex reveals a signal integration code in prostate cancer cells

*Department of Biological Sciences, Research Center for Functional Cellulomics and
^‡School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, South Korea;
^§Department of Biological Sciences, Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, South Korea; and
^†Department of Medical Sciences, Inha University, Incheon 402-751, South Korea

Communicated by Michael G. Rosenfeld, University of California at San Diego, La Jolla, CA, November 6, 2007 (received for review July 20, 2007)

Abstract

Posttranslational modification by small ubiquitin-like modifier (SUMO) controls diverse cellular functions of transcription factors and coregulators and participates in various cellular processes including signal transduction and transcriptional regulation. Here, we report that pontin, a component of chromatin-remodeling complexes, is SUMO-modified, and that SUMOylation of pontin is an active control mechanism for the transcriptional regulation of pontin on androgen-receptor target genes in prostate cancer cells. Biochemical purification of pontin-containing complexes revealed the presence of the Ubc9 SUMO-conjugating enzyme that underlies its function as an activator. Intriguingly, 5α-dihydroxytestosterone treatments significantly increased the SUMOylation of pontin, and SUMOylated pontin showed further activation of a subset of nuclear receptor-dependent transcription and led to an increase in proliferation and growth of prostate cancer cells. These data clearly define a functional model and provide a link between SUMO modification and prostate cancer progression.

Footnotes

^¶To whom correspondence should be addressed. E-mail: sbaek{at}snu.ac.kr
Author contributions: J.H.K. and S.H.B. designed research; J.H.K., J.M.L., H.J.N., H.J.C., J.W.Y., and M.H.K. performed research; J.S.L., S.-I.K., and C.H.C. contributed new reagents/analytic tools; J.H.K., K.I.K., S.H.B. analyzed data; and S.H.B. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0710343105/DC1.