Prospero-related homeobox 1 (Prox1) functions as a novel modulator of retinoic acid-related orphan receptors α- and γ-mediated transactivation.

ABSTRACT: In this study, we identify Prospero-related homeobox 1 (Prox1) as a novel co-repressor of the retinoic acid-related orphan receptors, RORα and RORγ. Prox1 interacts directly with RORγ and RORα and negatively regulates their transcriptional activity. The AF2 domain of RORs is essential for the interaction, whereas Prox1 interacts with RORs through either its 28 amino acids N-terminal region or its C-terminal prospero-like domain. RORγ antagonists stabilize the interaction between RORγ and Prox1. The homeodomain and the interaction through the prospero-like domain of Prox1 are critical for its repression of ROR transcriptional activity. Chromatin immunoprecipitation analysis demonstrated that in liver, Prox1 is recruited to the ROR response element sites of the clock genes, brain and muscle

SUBMITTER: Takeda Y 

PROVIDER: S-EPMC3737549 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature