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This version published online on March 27, 2003
Molecular Endocrinology, doi:10.1210/me.2002-0209
Molecular Endocrinology Vol. 0, No. 2003 200202091-
doi:10.1210/me.2002-0209
Copyright © 2003 by the Endocrine Society.
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*Compound via MeSH
*Substance via MeSH

Submitted on June 6, 2002
Accepted on March 18, 2003

Specific Ubiquitin-Conjugating Enzymes Promote Degradation of Specific Nuclear Receptor Coactivators

Feng Yan1, Xiuhua Gao1, David M. Lonard1, and Zafar Nawaz1*

1 Department of Surgery, Medical Microbiology & Immunology and Cancer Center Criss II, Room 518, Creighton University, 2500 California Plaza, Omaha, NE 68178, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

* To whom correspondence should be addressed. E-mail: znawaz{at}creighton.edu.

Nuclear receptor coactivators (NRCoA) are nuclear hormone receptor-associated regulatory proteins which interact with members of the nuclear receptor superfamily in the presence of their cognate ligand, enhancing their transcriptional activity. The identification of ubiquitin-proteasome pathway proteins as coactivators provides evidence that ubiquitin-proteasome mediated protein degradation plays an integral role in eukaryotic gene transcription. It has also been observed that nuclear receptors themselves are ubiquitinated and degraded in a hormone-dependent manner and that ubiquitin-proteasome function is essential for most nuclear receptors to function as transactivators. Here, we show that specific ubiquitin-proteasome pathway enzymes target specific NRCoA proteins in vivo and in vitro. First, using a temperature sensitive cell line that contains a thermolabile ubiquitin-activating E1 enzyme, we confirmed that NRCoA proteins are targets of the ubiquitin-proteasome pathway. Then using co-immunoprecipitation studies, we also demonstrate that in vivo, NRCoA proteins are ubiquitinated. Finally, we illustrate that in vitro, NRCoA ubiquitination and degradation depends on the ubiquitin-activating enzyme (E1) and on specific ubiquitin-conjugating enzymes (E2) for each of the coactivators.
Key words: NRCoA; ubiquitination; degradation

NURSA Molecule Pages Link:

Coregulators:   E6AP  |  UBCH7  |  CBP  |  SRC-1  |  GRIP1  |  AIB1



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