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Molecular and Cellular Biology, October 2004, p. 8716-8726, Vol. 24, No. 19
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.19.8716-8726.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Ubiquitin-Conjugating Enzyme UBCH7 Acts as a Coactivator for Steroid Hormone Receptors

Seema Verma ,^1,, Ayesha Ismail,^1, Xiuhua Gao,¹ Guilian Fu,¹ Xiaotao Li,² Bert W. O'Malley,² and Zafar Nawaz^1*

Cancer Center, Criss III, Creighton University, Omaha, Nebraska,¹ Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas²

Received 6 November 2003/ Returned for modification 2 December 2003/ Accepted 17 June 2004

We investigated the role of the ubiquitin-conjugating enzyme UBCH7 in nuclear receptor transactivation. Using transient transfection assays, we demonstrated that UBCH7 modulates the transcriptional activity of progesterone receptor (PR) and glucocorticoid, androgen, and retinoic acid receptors in a hormone-dependent manner and that the ubiquitin conjugation activity of UBCH7 is required for its ability to potentiate transactivation by steroid hormone receptors (SHR). However, UBCH7 showed no significant effect on the transactivation functions of p53 and VP-16 activation domain. Depletion of endogenous UBCH7 protein by small interfering RNAs suggests that UBCH7 is required for the proper function of SHR. Furthermore, a chromatin immunoprecipitation assay demonstrated the hormone-dependent recruitment of UBCH7 onto estrogen receptor- and PR-responsive promoters. Additionally, we show that UBCH7 and E6-associated protein (E6-AP) synergistically enhance PR transactivation. We also demonstrate that UBCH7 interacts with steroid receptor coactivator 1 (SRC-1) and that UBCH7 coactivation function is dependent on SRC-1. Taken together, our results reveal the possible role of UBCH7 in steroid receptor transactivation and provide insights into the mechanism of action of UBCH7 in receptor function.

S.V. and A.I. contributed equally to this work.

Present address: Battelle Pacific Northwest National Laboratory, Richland, Wash.

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