HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 46, 45340-45351, November 14, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/46/45340    most recent M303644200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Litterst, C. M. Articles by Pfitzner, E. Search for Related Content PubMed PubMed Citation Articles by Litterst, C. M. Articles by Pfitzner, E. Social Bookmarking                      What's this?

NCoA-1/SRC-1 Is an Essential Coactivator of STAT5 That Binds to the FDL Motif in the -Helical Region of the STAT5 Transactivation Domain^*

Claudia M. Litterst, Stefanie Kliem, Dominique Marilley, and Edith Pfitzner

From the Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Strasse 42-44, 60596 Frankfurt, Germany

Signal transducer and activator of transcription 5 (STAT5) is a transcription factor that activates prolactin (PRL)-dependent gene expression in the mammary gland. For the activation of its target genes, STAT5 recruits coactivators like p300 and the CREB-binding protein (CBP). In this study we analyzed the function of p300/CBP-associated members of the p160/SRC/NCoA-family in STAT5-mediated transactivation of -casein expression. We found that only one of them, NCoA-1, acts as a coactivator for both STAT5a and STAT5b. The two coactivators p300/CBP and NCoA-1 cooperatively enhance STAT5a-mediated transactivation. For NCoA-1-dependent coactivation of STAT5, both the activation domain 1 and the amino-terminal bHLH/PAS domain are required. The amino-terminal region mediates the interaction with STAT5a in cells. A motif of three amino acids in an -helical region of the STAT5a-transactivation domain is essential for the binding of NCoA-1 and for the transcriptional activity of STAT5a. Moreover we observed that NCoA-1 is involved in the synergistic action of the glucocorticoid receptor and STAT5a on the -casein promoter. These findings support a model in which STAT5, in concert with the glucocorticoid receptor, recruits a multifunctional coactivator complex to initiate the PRL-dependent transcription.

Received for publication, April 8, 2003 , and in revised form, August 22, 2003.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Strasse 42-44, 60596 Frankfurt, Germany. Tel.: 49-69-63395187; Fax: 49-69-63395297; E-mail: e.pfitzner{at}em.uni-frankfurt.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. D. Buzzelli, M. Nagarajan, J. F. Radtka, M. L. Shumate, M. Navaratnarajah, C. H. Lang, and R. N. Cooney Nuclear Factor-{kappa}B Mediates the Inhibitory Effects of Tumor Necrosis Factor-{alpha} on Growth Hormone-Inducible Gene Expression in Liver Endocrinology, December 1, 2008; 149(12): 6378 - 6388. [Abstract] [Full Text] [PDF]

				S.-H. Tan and M. T Nevalainen Signal transducer and activator of transcription 5A/B in prostate and breast cancers Endocr. Relat. Cancer, June 1, 2008; 15(2): 367 - 390. [Abstract] [Full Text] [PDF]

				M. A. Kleinschmidt, G. Streubel, B. Samans, M. Krause, and U.-M. Bauer The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation Nucleic Acids Res., June 1, 2008; 36(10): 3202 - 3213. [Abstract] [Full Text] [PDF]

				B. Basham, M. Sathe, J. Grein, T. McClanahan, A. D'Andrea, E. Lees, and A. Rascle In vivo identification of novel STAT5 target genes Nucleic Acids Res., June 1, 2008; 36(11): 3802 - 3818. [Abstract] [Full Text] [PDF]

				M. Lodrini, T. Munz, N. Coudevylle, C. Griesinger, S. Becker, and E. Pfitzner p160/SRC/NCoA coactivators form complexes via specific interaction of their PAS-B domain with the CID/AD1 domain Nucleic Acids Res., April 1, 2008; 36(6): 1847 - 1860. [Abstract] [Full Text] [PDF]

				O. M. Vidal, R. Merino, E. Rico-Bautista, L. Fernandez-Perez, D. J. Chia, J. Woelfle, M. Ono, B. Lenhard, G. Norstedt, P. Rotwein, et al. In Vivo Transcript Profiling and Phylogenetic Analysis Identifies Suppressor of Cytokine Signaling 2 as a Direct Signal Transducer and Activator of Transcription 5b Target in Liver Mol. Endocrinol., January 1, 2007; 21(1): 293 - 311. [Abstract] [Full Text] [PDF]

				J. Vanselow, W. Yang, J. Herrmann, H. Zerbe, H.-J. Schuberth, W. Petzl, W. Tomek, and H.-M. Seyfert DNA-remethylation around a STAT5-binding enhancer in the {alpha}S1-casein promoter is associated with abrupt shutdown of {alpha}S1-casein synthesis during acute mastitis J. Mol. Endocrinol., December 1, 2006; 37(3): 463 - 477. [Abstract] [Full Text] [PDF]

				R. W. E. Clarkson, M. P. Boland, E. A. Kritikou, J. M. Lee, T. C. Freeman, P. G. Tiffen, and C. J. Watson The Genes Induced by Signal Transducer and Activators of Transcription (STAT)3 and STAT5 in Mammary Epithelial Cells Define the Roles of these STATs in Mammary Development Mol. Endocrinol., March 1, 2006; 20(3): 675 - 685. [Abstract] [Full Text] [PDF]

				D. J. Chia, M. Ono, J. Woelfle, M. Schlesinger-Massart, H. Jiang, and P. Rotwein Characterization of Distinct Stat5b Binding Sites That Mediate Growth Hormone-stimulated IGF-I Gene Transcription J. Biol. Chem., February 10, 2006; 281(6): 3190 - 3197. [Abstract] [Full Text] [PDF]

				D. Neculai, A. M. Neculai, S. Verrier, K. Straub, K. Klumpp, E. Pfitzner, and S. Becker Structure of the Unphosphorylated STAT5a Dimer J. Biol. Chem., December 9, 2005; 280(49): 40782 - 40787. [Abstract] [Full Text] [PDF]

				Z. Gao, P. Chiao, X. Zhang, X. Zhang, M. A. Lazar, E. Seto, H. A. Young, and J. Ye Coactivators and Corepressors of NF-{kappa}B in I{kappa}B{alpha} Gene Promoter J. Biol. Chem., June 3, 2005; 280(22): 21091 - 21098. [Abstract] [Full Text] [PDF]

				R.-C. Wu, C. L. Smith, and B. W. O'Malley Transcriptional Regulation by Steroid Receptor Coactivator Phosphorylation Endocr. Rev., May 1, 2005; 26(3): 393 - 399. [Abstract] [Full Text] [PDF]

				T. Valineva, J. Yang, R. Palovuori, and O. Silvennoinen The Transcriptional Co-activator Protein p100 Recruits Histone Acetyltransferase Activity to STAT6 and Mediates Interaction between the CREB-binding Protein and STAT6 J. Biol. Chem., April 15, 2005; 280(15): 14989 - 14996. [Abstract] [Full Text] [PDF]

				N. Yin, D. Wang, H. Zhang, X. Yi, X. Sun, B. Shi, H. Wu, G. Wu, X. Wang, and Y. Shang Molecular Mechanisms Involved in the Growth Stimulation of Breast Cancer Cells by Leptin Cancer Res., August 15, 2004; 64(16): 5870 - 5875. [Abstract] [Full Text] [PDF]

				Y. Wang, M. G. Malabarba, Z. S. Nagy, and R. A. Kirken Interleukin 4 Regulates Phosphorylation of Serine 756 in the Transactivation Domain of Stat6: ROLES FOR MULTIPLE PHOSPHORYLATION SITES AND Stat6 FUNCTION J. Biol. Chem., June 11, 2004; 279(24): 25196 - 25203. [Abstract] [Full Text] [PDF]