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Molecular and Cellular Biology, December 2005, p. 10442-10453, Vol. 25, No. 23
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.23.10442-10453.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

SF-1 (Nuclear Receptor 5A1) Activity Is Activated by Cyclic AMP via p300-Mediated Recruitment to Active Foci, Acetylation, and Increased DNA Binding

Wei-Yi Chen,1,2 Li-Jung Juan,3 and Bon-chu Chung1*

Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan,1 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan,2 President Laboratory, National Health Research Institutes, Miaoli, Taiwan3

Received 15 June 2005/ Returned for modification 8 July 2005/ Accepted 19 September 2005

Steroidogenic factor 1 (SF-1) is a nuclear receptor essential for steroidogenic gene expression, but how its activity is regulated is unclear. Here we demonstrate that p300 plays an important role in regulating SF-1 function. SF-1 was acetylated in vitro and in vivo by p300 at the KQQKK motif in the Ftz-F1 (Fushi-tarazu factor 1) box adjacent to its DNA-binding domain. Mutation of the KQQKK motif reduced the DNA-binding activity and p300-dependent activation of SF-1. When stimulated with cyclic AMP (cAMP), adrenocortical Y1 cells expressed more p300, leading to additional SF-1 association with p300 and increased SF-1 acetylation and DNA binding. It also increased SF-1 colocalization with p300 in nuclear foci. Collectively, these results indicate that SF-1 transcriptional activity is regulated by p300 in response to the cAMP signaling pathway by way of increased acetylation, DNA binding, and recruitment to nuclear foci.

* Corresponding author. Mailing address: Institute of Molecular Biology, 48, Academia Sinica, Nankang, Taipei 115, Taiwan. Phone: 886-2-2789 9215. Fax: 886-2-2782 6085. E-mail: mbchung{at}sinica.edu.tw.

Molecular and Cellular Biology, December 2005, p. 10442-10453, Vol. 25, No. 23
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.23.10442-10453.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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