| Modification Notes |
Retinoids are metabolites of vitamin A (retinol) and represent important signaling molecules during vertebrate development and tissue differentiation. Retinoic acid receptors (RARs) have a high affinity for all trans-retinoic acids and belong to the same class of nuclear transcription factors as thyroid hormone receptors, vitamin D3 receptor and ecdysone receptor. Two cofactors that function to repress transcription, designated SMRT (silencing mediator for RARs and thyroid receptors (TR)) and N-CoR, associate with TR and RAR in their unliganded state and are released from them upon ligand binding. The carboxy-termini of both proteins contain receptor interacting domains while their amino-termini contain two repressor domains. SMRT is comprised of 1,495 amino acids and contains an 8 amino acid sequence that is not present in SMRTe (SMRT-extended), which contains 2,514 amino acids. SMRTe contains an N-terminal sequence spanning over 1,000 amino acids that is not present in SMRT, but that shows significant similarity with N-CoR. SMRTe expression is regulated during cell cycle progression, suggesting a role for SMRTe in the regulation of cycle-specific gene expression in diverse signaling pathways. |
