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Modulation of Androgen Receptor Transactivation by the SWI3-Related Gene Product (SRG3) in Multiple Ways

Cheol Yi Hong,^1,2, Ji Ho Suh,^1,2, Kabsun Kim,^1,2 Eun-Yeung Gong,^1,2 Sung Ho Jeon,³ Myunggon Ko,³ Rho Hyun Seong,³ Hyuk Bang Kwon,^1,2 and Keesook Lee^1,2*

Hormone Research Center,¹ School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Republic of Korea,² School of Biological Sciences and Institute of Molecular Biology & Genetics, Seoul National University, Seoul 151-742, Republic of Korea³

Received 13 July 2004/ Returned for modification 20 August 2004/ Accepted 10 March 2005

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.

The first two authors contributed equally to the work.

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