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Molecular and Cellular Biology, March 2007, p. 2027-2036, Vol. 27, No. 6
0270-7306/07/$08.00+0     doi:10.1128/MCB.02253-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cyclic AMP Stimulates SF-1-Dependent CYP11A1 Expression through Homeodomain-Interacting Protein Kinase 3-Mediated Jun N-Terminal Kinase and c-Jun Phosphorylation{triangledown}

Hsin-Chieh Lan,1,2 Hua-Jung Li,1,2 Guang Lin,1 Pao-Yen Lai,1,3 and Bon-chu Chung1,2*

Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan,1 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan,2 Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan3

Received 1 December 2006/ Accepted 19 December 2006

Steroids are synthesized in adrenal glands and gonads under the control of pituitary peptides. These peptides bind to cell surface receptors to activate the cyclic AMP (cAMP) signaling pathway leading to an increase of steroidogenic gene expression. Exactly how cAMP activates steroidogenic gene expression is not clear, except for the knowledge that transcription factor SF-1 plays a key role. Investigating the factors participating in SF-1 action, we found that c-Jun and homeodomain-interacting protein kinase 3 (HIPK3) were required for basal and cAMP-stimulated expression of one major steroidogenic gene, CYP11A1. HIPK3 enhanced SF-1 activity, and c-Jun was required for the functional interaction of HIPK3 with SF-1. Furthermore, after cAMP stimulation, both c-Jun and Jun N-terminal kinase (JNK) were phosphorylated through HIPK3. These phosphorylations were important for SF-1 activity and CYP11A1 expression. Thus, we have defined HIPK3-mediated JNK activity and c-Jun phosphorylation as important events that increase SF-1 activity for CYP11A1 transcription in response to cAMP. This finding has linked three common factors, HIPK3, JNK, and c-Jun, to the cAMP signaling pathway leading to increased steroidogenic gene expression.


* Corresponding author. Mailing address: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan. Phone: 886-2-2789 9215. Fax: 886-2-2788 3464. E-mail: mbchung{at}sinica.edu.tw.

{triangledown} Published ahead of print on 8 January 2007.


Molecular and Cellular Biology, March 2007, p. 2027-2036, Vol. 27, No. 6
0270-7306/07/$08.00+0     doi:10.1128/MCB.02253-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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