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Molecular and Cellular Biology, March 2000, p. 1855-1867, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mouse Zac1, a Transcriptional Coactivator and Repressor for Nuclear Receptors

Shih-Ming Huang and Michael R. Stallcup*

Departments of Pathology and of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90089

Received 28 July 1999/Returned for modification 28 September 1999/Accepted 29 November 1999

Transcriptional activation by nuclear hormone receptors is mediated by the 160-kDa family of nuclear receptor coactivators. These coactivators associate with DNA-bound nuclear receptors and transmit activating signals to the transcription machinery through two activation domains. In screening for mammalian proteins that bind the C-terminal activation domain of the nuclear receptor coactivator GRIP1, we identified a new variant of mouse Zac1 which we call mZac1b. Zac1 was previously discovered as a putative transcriptional activator involved in regulation of apoptosis and the cell cycle. In yeast two-hybrid assays and in vitro, mZac1b bound to GRIP1, to CREB-binding protein (CBP) and p300 (which are coactivators for nuclear receptors and other transcriptional activators), and to nuclear receptors themselves in a hormone-independent manner. In transient-transfection assays mZac1b exhibited a transcriptional activation activity when fused with the Gal4 DNA binding domain, and it enhanced transcriptional activation by the Gal4 DNA binding domain fused to GRIP1 or CBP fragments. More importantly, mZac1b was a powerful coactivator for the hormone-dependent activity of nuclear receptors, including androgen, estrogen, glucocorticoid, and thyroid hormone receptors. However, with some reporter genes and in some cell lines mZac1b acted as a repressor rather than a coactivator of nuclear receptor activity. Thus, mZac1b can interact with nuclear receptors and their coactivators and play both positive and negative roles in regulating nuclear receptor function.


* Corresponding author. Mailing address: Dept. of Pathology, HMR 301, University of Southern California, 2011 Zonal Ave., Los Angeles, CA 90089. Phone: (323) 442-1289. Fax: (323) 442-3049. E-mail: stallcup{at}hsc.usc.edu.


Molecular and Cellular Biology, March 2000, p. 1855-1867, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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