Receptor-interacting protein 140 differentially regulates estrogen receptor-related receptor transactivation depending on target genes.
We have investigated the effects of receptor-interacting protein 140 (RIP140) on transcriptional regulation by estrogen receptor-related receptors (ERRs). We first show that RIP140 inhibits transactivation by ERRalpha, beta, and gamma on natural or artificial reporter genes containing different types of response elements. This repression correlates with a strong in vitro binding between several regions of RIP140 and the three ERR isoforms. Surprisingly, although RIP140 inhibits transactivation of the thyroid hormone receptor-alpha gene by ERRbeta, it significantly increases its regulation by ERRalpha and ERRgamma. Mutagenesis and transient transfections in SL2 cells indicate that thyroid hormone receptor-alpha promoter expression involved Sp1 sites. In support of this observation, we demonstrate that RIP140 also positively regulates ERRs transactivation of other known Sp1 targets such as the p21 gene. This effect requires the two proximal Sp1 binding sites of the promoter and is partially dependent on the activation function 2 domain of ERRs. Finally, we provide evidences for a role of histone deacetylases in the regulation of p21 promoter by RIP140. Altogether, these data indicate that RIP140 differentially regulates ERR activity depending on the target sequence on the promoters.
Castet
Audrey
A
Institut National de la Santé et de la Recherche Médicale Unité 540, Endocrinologie Moléculaire et Cellulaire des Cancers and Université de Montpellier I, 60 rue de Navacelles, 34090 Montpellier, France.
Herledan
Adrien
A
Bonnet
Sandrine
S
Jalaguier
Stéphan
S
Vanacker
Jean-Marc
JM
Cavaillès
Vincent
V
D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000078723:Nuclear Receptor Interacting Protein 1; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000097983:ERRalpha Estrogen-Related Receptor
D048868:Adaptor Proteins, Signal Transducing; D006655:Histone Deacetylases; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D016329:Sp1 Transcription Factor; D037021:Thyroid Hormone Receptors alpha; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D000097983:ERRalpha Estrogen-Related Receptor; C490918:ESRRB protein, human; C490917:ESRRG protein, human; C000627127:NRIP1 protein, human; C051838:TFF1 protein, human