PMID- 15367689 OWN - NLM STAT- MEDLINE DCOM- 20041101 LR - 20181113 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 24 IP - 19 DP - 2004 Oct TI - The ubiquitin-conjugating enzyme UBCH7 acts as a coactivator for steroid hormone receptors. PG - 8716-26 AB - 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. FAU - Verma, Seema AU - Verma S AD - Cancer Center, Criss III, Room 352, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA. FAU - Ismail, Ayesha AU - Ismail A FAU - Gao, Xiuhua AU - Gao X FAU - Fu, Guilian AU - Fu G FAU - Li, Xiaotao AU - Li X FAU - O'Malley, Bert W AU - O'Malley BW FAU - Nawaz, Zafar AU - Nawaz Z LA - eng GR - R01 DK056833/DK/NIDDK NIH HHS/United States GR - R01 HD008188/HD/NICHD NIH HHS/United States GR - HD-08188/HD/NICHD NIH HHS/United States GR - DK56833/DK/NIDDK NIH HHS/United States GR - F32 HD008188/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - 0 (Receptors, Steroid) RN - 0 (Transcription Factors) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 2.3.2.23 (UBE2L3 protein, human) RN - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes) RN - EC 2.3.2.26 (UBE3A protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Gene Expression Regulation/physiology MH - HeLa Cells MH - Histone Acetyltransferases MH - Humans MH - Nuclear Receptor Coactivator 1 MH - Promoter Regions, Genetic MH - Receptors, Estrogen/genetics/metabolism MH - Receptors, Progesterone/genetics/metabolism MH - Receptors, Steroid/genetics/*metabolism MH - Transcription Factors/metabolism MH - Transcription, Genetic MH - Ubiquitin-Conjugating Enzymes/*metabolism MH - Ubiquitin-Protein Ligases/metabolism PMC - PMC516762 EDAT- 2004/09/16 05:00 MHDA- 2004/11/02 09:00 PMCR- 2004/10/01 CRDT- 2004/09/16 05:00 PHST- 2004/09/16 05:00 [pubmed] PHST- 2004/11/02 09:00 [medline] PHST- 2004/09/16 05:00 [entrez] PHST- 2004/10/01 00:00 [pmc-release] AID - 24/19/8716 [pii] AID - 1770-03 [pii] AID - 10.1128/MCB.24.19.8716-8726.2004 [doi] PST - ppublish SO - Mol Cell Biol. 2004 Oct;24(19):8716-26. doi: 10.1128/MCB.24.19.8716-8726.2004.