| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 13, 2006
Accepted on January 2, 2007
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan; Department of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan
* To whom correspondence should be addressed. E-mail: iguo{at}ntu.edu.tw.
The CYP11A1 encodes cytochrome P450scc catalyzing the first step of steroidogenesis in adrenals and gonads under the control of cAMP-mediated hormonal signals. The cAMP-induced activation of human CYP11A1 has been suggested to depend on the transcription factor CREB, but the CREB action can not explain the chronic cAMP effect on CYP11A1 activation. To further understand the mechanism of human CYP11A1 activation, we dissected the functions of the upstream cAMP responsive sequences (U-CRS) containing a core sequence, U identical to the SF-1-binding site, and two flanking TRE/CRE-like elements, C1 and C2. The EMSA assays showed that the binding activities of U with SF-1 as well as C1 or C2 with AP-1/CREB-like proteins are induced by cAMP. The results from the site-directed mutagenesis analyses revealed that all three elements are required for the U-CRS function and any mutation of C1, C2, or U impairs the response to cAMP stimulation. In transgenic mice, the single or double mutations of C1 and C2 resulted in the reduction of reporter gene expression accompanied with poor hormonal response. The cAMP induction on the U-CRS activity was mimicked and enhanced by the over-expressed c-Jun in the presence of SF-1, but was abolished by the over-expression of an AP-1 dominant negative mutant, FosB2. Furthermore, we have observed the interdependent transactivation between SF-1 and c-Jun on the U-CRS function. These results collectively demonstrate that SF-1 and AP-1 cooperate to activate CYP11A1 transcription in vitro and in vivo.
This article has been cited by other articles:
 |
|
 |
|
  S. L. Poon, B.-S. An, W.-K. So, G. L. Hammond, and P. C. K. Leung Temporal Recruitment of Transcription Factors at the 3',5'-Cyclic Adenosine 5'-Monophosphate-Response Element of the Human GnRH-II Promoter Endocrinology, October 1, 2008; 149(10): 5162 - 5171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-C. Shih, N.-C. Hsu, C.-C. Huang, T.-S. Wu, P.-Y. Lai, and B.-c. Chung Mutation of Mouse Cyp11a1 Promoter Caused Tissue-Specific Reduction of Gene Expression and Blunted Stress Response without Affecting Reproduction Mol. Endocrinol., April 1, 2008; 22(4): 915 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. E. Beshay, J. C. Havelock, R. Sirianni, P. Ye, T. Suzuki, W. E. Rainey, and B. R. Carr The Mechanism for Protein Kinase C Inhibition of Androgen Production and 17{alpha}-Hydroxylase Expression in a Theca Cell Tumor Model J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4802 - 4809. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
