| Notes
|
Data describe a 17 residue fragment from SMRT that binds to the BCL6 BTB domain, and report the crystal structure of the complex to 2.2 angstroms. Differing transcriptional properties appear to reflect the differing abilities of the three RAR isotypes to interact with the SMRT corepressor protein. Elevated SMRT levels are common in prostate cancer cells, resulting in suppression of target genes associated with antiproliferative action. Interactions that determine the assembly of a retinoid X receptor/corepressor complex. N-CoR and SMRT play an active role in preventing tamoxifen from stimulating proliferation in breast cancer cells through repression of a subset of target genes involved in ERalpha function and cell proliferation. No significant allelic/genotypic association between any of the five mutations in SMRT/N-CoR2 and bipolar phenotype and the CAG repeat did not demonstrate allelic instability. SANT motif interprets the histone code and promotes histone deacetylation. SMRT and DAX-1 repress agonist-dependent activity of both androgen and progesterone receptors. SMRT has a role as a coactivator for thyroid hormone receptor T3Ralpha from a negative hormone response element. SMRTbeta expression may influence the binding and transcriptional capacities of nuclear receptors in tumor cells (SMRTbeta). Sstable binding of the Stat5-RARalpha fusion protein to corepressor SMRT is accompanied by an impaired response to differentiation signals in hematopoietic cells. TRAC-1 (T cell RING protein identified in activation screen)is the first E3 ubiquitin ligase that serves a positive regulatory role in T cell activation. The silencing mediator of retinoic acid and thyroid hormone receptors can interact with the aryl hydrocarbon (Ah) receptor but fails to repress Ah receptor-dependent gene expression. A significant role of SMRT in modulating androgen receptor transcriptional activity. Differential mRNA splicing of SMRT serves to customize corepressor function in different cells, allowing the transcriptional properties of nuclear receptors to be adapted to different contexts. Differential recruitment of steroid receptor coactivator-1 and silencing mediator for retinoid and thyroid receptors by estrogen receptor-alpha and beta in breast cancer may be central to the response of the tumor to endocrine treatment. The effect of STAT5b-RARalpha on the activity of myeloid transcription factors including STAT3, and STAT5 as well as its molecular interactions with the nuclear receptor corepressor, SMRT, and nuclear receptor coactivator, TRAM-1. The subnuclear positioning of SMRT is influenced by the ligand-bound ERalpha, and this activity is dependent on the ratio of the co-expressed ERalpha and SMRT.
|