SUMOylation of pontin chromatin-remodeling complex reveals a signal integration code in prostate cancer cells.
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, 5alpha-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.
Kim
Jung Hwa
JH
Department of Biological Sciences, Research Center for Functional Cellulomics and School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, South Korea.
Lee
Ji Min
JM
Nam
Hye Jin
HJ
Choi
Hee June
HJ
Yang
Jung Woo
JW
Lee
Jason S
JS
Kim
Mi Hyang
MH
Kim
Su-Il
SI
Chung
Chin Ha
CH
Kim
Keun Il
KI
Baek
Sung Hee
SH
D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000737:chemistry*; D004265:DNA Helicases / Q000737:chemistry*; D006801:Humans; D006915:Hydroxytestosterones / Q000494:pharmacology; D008239:Lysine / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000378:metabolism*; D025842:SUMO-1 Protein; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry*; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D002352:Carrier Proteins; D002843:Chromatin; D006915:Hydroxytestosterones; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D008239:Lysine