Modulation of androgen receptor transactivation by the SWI3-related gene product (SRG3) in multiple ways.
The SWI3-related gene product (SRG3), a component of the mouse SWI/SNF complex, has been suggested to have an alternative function. Here, we demonstrate that in the prostate transactivation of the androgen receptor (AR) is modulated by SRG3 in multiple ways. The expression of SRG3, which is developmentally regulated in the prostate, is induced by androgen through AR. SRG3 in turn enhances the transactivation of AR, providing a positive feedback regulatory loop. The SRG3 coactivation of AR transactivation is achieved through the recruitment of coactivator SRC-1, the protein level of which is upregulated by SRG3, providing another pathway of positive regulation. Interestingly, SRG3 coactivation of AR transactivation is fully functional in BRG1/BRM-deficient C33A cells and the AR/SRG3/SRC-1 complex formed in vivo contains neither BRG1 nor BRM protein, suggesting the possibility of an SRG3 function independent of the SWI/SNF complex. Importantly, the AR/SRG3/SRC-1 complex occupies androgen response elements on the endogenous SRG3 and PSA promoter in an androgen-dependent manner in mouse prostate and LNCaP cells, respectively, inducing gene expression. These results suggest that the multiple positive regulatory mechanisms of AR transactivation by SRG3 may be important for the rapid proliferation of prostate cells during prostate development and regeneration.
Hong
Cheol Yi
CY
Hormone Research Center and School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
Suh
Ji Ho
JH
Kim
Kabsun
K
Gong
Eun-Yeung
EY
Jeon
Sung Ho
SH
Ko
Myunggon
M
Seong
Rho Hyun
RH
Kwon
Hyuk Bang
HB
Lee
Keesook
K
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D051548:Histone Acetyltransferases; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D056920:Nuclear Receptor Coactivator 1; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011944:Receptors, Androgen; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C111382:NCOA4 protein, human; C491090:Smarcc1 protein, mouse; C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse