Corepressors: custom tailoring and alterations while you wait

Michael Goodson
2005 Nuclear Receptor Signaling  
A diverse cadre of metazoan transcription factors mediate repression by recruiting protein complexes containing the SMRT (silencing mediator of retinoid and thyroid hormone receptor) or N-CoR (nuclear receptor corepressor) corepressors. SMRT and N-CoR nucleate the assembly of still larger corepressor complexes that perform the specific molecular incantations necessary to confer transcriptional repression. Although SMRT and N-CoR are paralogs and possess similar molecular architectures and
more » ... istic strategies, they nonetheless exhibit distinct molecular and biological properties. It is now clear that the functions of both SMRT and N-CoR are further diversified through alternative mRNA splicing, yielding a series of corepressor protein variants that participate in distinctive transcription factor partnerships and display distinguishable repression properties.This review will discuss what is known about the structure and actions of SMRT, N-CoR, and their splicing variants, and how alternative splicing may allow the functions of these corepressors to be adapted and tailored to different cells and to different developmental stages. | Abbreviations: BCL-6: B-cell leukemia protein-6; B-Myb: B locus of cellular myeloblastosis oncogene; CBF-1: CCAAT-box binding factor; CoRNR box: CoR-nuclear receptor interaction box; DAD: deacetylase activating domain; ETO-1/2: eight/twenty one translocation protein-1/2; GPS-2: G protein suppressor-2; HDAC: histone deacetylase; MAPK: mitogen-activated protein kinase; MEKK1: MAP/ERK protein kinase kinase-1; MyoD: myoblast determination protein; N-CoR: nuclear receptor corepressor; NF-κB: nuclear transcription factor κ B; Oct-1: octamer-element binding factor-1; Pit-1: pituitary transcription factor-1; PLZF: promyelocytic zinc-finger protein; RAR: retinoic acid receptor; RD: repression domain; RIP13: receptor interacting protein 13; SANT: SWI3, ADA2, N-CoR, and TFIIB related domain; SAP30: Sin3 associated protein 30; Sharp: SMRT/HDAC-1 associated protein; Siah-2: seven in absentia homolog-2; SMAD: SMA,/MAD related; SMRT: silencing mediator for retinoid-thyroid hormone receptors; SRF: serum response factor; TAFII-32/70: TATA-binding protein associated factor-32/70; TBL-1: transducin B-like protein-1; TBLR-1: TBL-related protein-1; TFIIB: transcription factor IIB; TR: thyroid hormone receptor; TRAC: TR/RAR associated cofactor |
doi:10.1621/nrs.03003 pmid:16604171 pmcid:PMC1402215 fatcat:524njiubt5evxkpjtinsp5eljq