PMID- 19350571 OWN - NLM STAT- MEDLINE DCOM- 20090901 LR - 20211020 IS - 1097-4644 (Electronic) IS - 0730-2312 (Print) IS - 0730-2312 (Linking) VI - 107 IP - 3 DP - 2009 Jun 1 TI - HACE1: A novel repressor of RAR transcriptional activity. PG - 482-93 LID - 10.1002/jcb.22146 [doi] AB - The diverse biological actions of retinoic acid (RA) are mediated by RA receptors (RARs) and retinoid X receptors (RXRs). While the coregulatory proteins that interact with the ligand-dependent AF-2 in the E region are well studied, the ligand-independent N-terminal AF-1 domain-interacting partners and their influence(s) on the function of RARs are poorly understood. HECT domain and Ankyrin repeat containing E3 ubiquitin-protein ligase (HACE1) was isolated as a RARbeta(3) AB region interacting protein. HACE1 interacts with RARbeta(3) both in in vitro GST pull-down and in cell-based coprecipitation assays. The interaction sites map to the N terminus of RARbeta(3) and the C terminus of HACE1. HACE1 functionally represses the transcriptional activity of RARalpha(1), RARbeta isoforms 1, 2, and 3, but not RARgamma(1) in luciferase reporter assays. In addition, HACE1 represses the endogenous RAR-regulated genes CRABP II, RIG1 and RARbeta(2), but not RAI3 in CAOV3 cells. Mutation of the putative catalytic cysteine (C876 of LF HACE1), which is indispensable for its E3 ubiquitin ligase activity, does not alter the repressive effect of HACE1 on the transcriptional activity of RARbeta(3). On the other hand, HACE1 inhibits the RA dependent degradation of RARbeta(3). It is possible that the repression of RAR-regulated transcription by HACE1 is due to its ability to inhibit the RA-dependent degradation of RARs. CI - (c) 2009 Wiley-Liss, Inc. FAU - Zhao, Jianhua AU - Zhao J AD - Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. FAU - Zhang, Zhenping AU - Zhang Z FAU - Vucetic, Zivjena AU - Vucetic Z FAU - Soprano, Kenneth J AU - Soprano KJ FAU - Soprano, Dianne Robert AU - Soprano DR LA - eng GR - R01 DK067558-02/DK/NIDDK NIH HHS/United States GR - DK67558/DK/NIDDK NIH HHS/United States GR - R01 CA064945/CA/NCI NIH HHS/United States GR - DK44517/DK/NIDDK NIH HHS/United States GR - R01 DK044517/DK/NIDDK NIH HHS/United States GR - CA64945/CA/NCI NIH HHS/United States GR - R01 DK067558/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Receptors, Retinoic Acid) RN - 0 (Repressor Proteins) RN - EC 2.3.2.26 (HACE1 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Animals MH - COS Cells MH - Chlorocebus aethiops MH - Humans MH - Mice MH - NIH 3T3 Cells MH - Receptors, Retinoic Acid/*metabolism MH - Repressor Proteins/genetics/*metabolism MH - *Transcription, Genetic MH - Ubiquitin-Protein Ligases/genetics/*metabolism PMC - PMC2736627 MID - NIHMS137018 EDAT- 2009/04/08 09:00 MHDA- 2009/09/02 06:00 PMCR- 2009/09/02 CRDT- 2009/04/08 09:00 PHST- 2009/04/08 09:00 [entrez] PHST- 2009/04/08 09:00 [pubmed] PHST- 2009/09/02 06:00 [medline] PHST- 2009/09/02 00:00 [pmc-release] AID - 10.1002/jcb.22146 [doi] PST - ppublish SO - J Cell Biochem. 2009 Jun 1;107(3):482-93. doi: 10.1002/jcb.22146.