| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
The Albert Einstein Cancer Center, Departments of Medicine and
Developmental and Molecular Biology Albert Einstein College of
Medicine Bronx, New York 10461
Department of Biology
(A.D., T.W.) Yale University New Haven, Connecticut 06520
Division of Endocrinology, Metabolism, and Molecular
Medicine (I-W.S.) Northwestern University Medical School
Chicago, Illinois 60611
The ovine P450 side chain cleavage (CYP11A1) enzyme gene, which catalyzes the initial enzymatic step in steroid hormone biosynthesis is transcriptionally regulated in cultured steroidogenic human trophoblastic JEG-3 cells. The ovine CYP11A1 promoter contains two GC-rich footprinted regions referred to as ovine footprints 5 (OF5) and OF3, which are well conserved among the CYP11A1 promoters of different species. These GC-rich sequences resemble activator protein-2 (AP-2)/Sp1 binding sites and were previously implicated in basal and cAMP-regulated activity of the bovine and ovine CYP11A1 promoters. In the current studies, AP-2 induced the ovine CYP11A1 promoter 4.5-fold in JEG-3 cells with full induction requiring the previously defined cAMP-responsive elements. Point mutation of OF3 abolished induction by AP-2, and OF3 was sufficient for induction by AP-2 when linked to a heterologous promoter. AP-2 induction of the CYP11A1 promoter required the basic region (N165-N278) and the carboxy terminus of AP-2 (N413-N437). In the course of investigating the mechanisms by which OF5 and OF3 regulated CYP11A1 transcription, we found that OF5 and OF3 bound Sp1 and Sp3 in JEG-3 cells. AP-2 did not bind OF5 or OF3 directly but rather formed a multiprotein complex with Sp1 in JEG-3 cells. AP-2 associated directly with Sp1 in vitro requiring the AP-2 basic region and the Sp1 carboxy terminus. AP-2 induced Sp1/Sp3 activity independently of AP-2 binding to DNA using a GAL4 paradigm. The Sp1 and Sp3 transactivation domains were linked to the DNA-binding domain of GAL4, and their activity was assessed using a luciferase reporter gene containing only the GAL4 DNA-binding sites linked to the minimal TATA site. AP-2 induced Sp1/Sp3-GAL4 activity 3- to 4-fold, requiring both the amino and extreme carboxy terminus of AP-2. We conclude that AP-2 can bind to and stimulate Sp1 activity and induces the ovine CYP11A1 promoter through conserved Sp1/Sp3-binding sites in JEG-3 cells. The induction of Sp1 activity by AP-2 may contribute to the induction of other genes that bind Sp1.
This article has been cited by other articles:
 |
|
 |
|
  F. Paonessa, D. Foti, V. Costa, E. Chiefari, G. Brunetti, F. Leone, F. Luciano, F. Wu, A. S. Lee, E. Gulletta, et al. Activator Protein-2 Overexpression Accounts for Increased Insulin Receptor Expression in Human Breast Cancer. Cancer Res., May 15, 2006; 66(10): 5085 - 5093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Natesampillai, M. E. Fernandez-Zapico, R. Urrutia, and J. D. Veldhuis A Novel Functional Interaction between the Sp1-like Protein KLF13 and SREBP-Sp1 Activation Complex Underlies Regulation of Low Density Lipoprotein Receptor Promoter Function J. Biol. Chem., February 10, 2006; 281(6): 3040 - 3047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zhang and J. D. Veldhuis Insulin Drives Transcriptional Activity of the CYP17 Gene in Primary Culturesof Swine Theca Cells Biol Reprod, June 1, 2004; 70(6): 1600 - 1605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Val, C. Aigueperse, B. Ragazzon, G. Veyssiere, A.-M. Lefrancois-Martinez, and A. Martinez Adrenocorticotropin/3',5'-Cyclic AMP-Mediated Transcription of the Scavenger akr1-b7 Gene in Adrenocortical Cells Is Dependent on Three Functionally Distinct Steroidogenic Factor-1-Responsive Elements Endocrinology, February 1, 2004; 145(2): 508 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Cheng and S. Handwerger Identification of an Enhancer of the Human Activating Protein-2{alpha} Gene That Contains a Critical Ets1 Binding Site J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3305 - 3311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Campillos, M. A. Garcia, F. Valdivieso, and J. Vazquez Transcriptional activation by AP-2{alpha} is modulated by the oncogene DEK Nucleic Acids Res., March 1, 2003; 31(5): 1571 - 1575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zhou and C.-M. Chiang Sp1 and AP2 regulate but do not constitute TATA-less human TAFII55 core promoter activity Nucleic Acids Res., October 1, 2002; 30(19): 4145 - 4157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ben-Zimra, M. Koler, and J. Orly Transcription of Cholesterol Side-Chain Cleavage Cytochrome P450 in the Placenta: Activating Protein-2 Assumes the Role of Steroidogenic Factor-1 by Binding to an Overlapping Promoter Element Mol. Endocrinol., August 1, 2002; 16(8): 1864 - 1880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fu, C. Wang, J. Wang, X. Zhang, T. Sakamaki, Y. G. Yeung, C. Chang, T. Hopp, S. A. W. Fuqua, E. Jaffray, et al. Androgen Receptor Acetylation Governs trans Activation and MEKK1-Induced Apoptosis without Affecting In Vitro Sumoylation and trans-Repression Function Mol. Cell. Biol., May 15, 2002; 22(10): 3373 - 3388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Auman, T. Nottoli, O. Lakiza, Q. Winger, S. Donaldson, and T. Williams Transcription factor AP-2{gamma} is essential in the extra-embryonic lineages for early postimplantation development Development, January 6, 2002; 129(11): 2733 - 2747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Blaine, M. Wick, C. Dessev, and R. A. Nemenoff Induction of cPLA2 in Lung Epithelial Cells and Non-small Cell Lung Cancer Is Mediated by Sp1 and c-Jun J. Biol. Chem., November 9, 2001; 276(46): 42737 - 42743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Terzano, A. Flora, F. Clementi, and D. Fornasari The Minimal Promoter of the Human alpha 3 Nicotinic Receptor Subunit Gene. MOLECULAR AND FUNCTIONAL CHARACTERIZATION J. Biol. Chem., December 22, 2000; 275(52): 41495 - 41503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ren and W. S.-L. Liao Transcription Factor AP-2 Functions as a Repressor That Contributes to the Liver-specific Expression of Serum Amyloid A1 Gene J. Biol. Chem., May 18, 2001; 276(21): 17770 - 17778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schuierer, K. Hilger-Eversheim, T. Dobner, A.-K. Bosserhoff, M. Moser, J. Turner, M. Crossley, and R. Buettner Induction of AP-2alpha Expression by Adenoviral Infection Involves Inactivation of the AP-2rep Transcriptional Corepressor CtBP1 J. Biol. Chem., July 20, 2001; 276(30): 27944 - 27949. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
