Regulation of SMRT and N-CoR corepressor function

M. L. Privalsky

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Investigators have just begun to understand how the functions of corepressors such as SMRT and N-CoR are regulated. Nonetheless, it is already clear that the actions of these corepressors are controlled at many different levels. The sequence and topology of the DNA response element define the nature of the nuclear receptor homo- or heterodimer recruited to a particular promoter. The nature of the nuclear receptor dimer can determine, in turn, the identity of the corepressor complex tethered to the receptor and the combinatorial effects of hormone ligand on corepressor retention or release. Different receptor isoforms can differ in the ability to recruit corepressors, and corepressors, once recruited, can be either functional or held inactive by additional contacts with the nuclear receptor. The precise shape of the hormone ligand can invoke different allosteric responses in the nuclear receptor that manifest as differences in the retinue of coactivators and corepressors that associate with the liganded receptor. Post-translational modifications can further influence the ability of the corepressor to tether to the receptor and to mediate transcriptional repression. Superimposed on these mechanisms are controls on the transcription, alternative mRNA splicing, and proteolytic degradation of the corepressors themselves. As alluded to earlier in this review, the nuclear receptors serve as signal processors and integrators. Corepressors represent a critical component of this signal processing machinery, serving both as a relay through which different signals can be input, and as an effector through which an output, transcriptional repression, can be manifested. In this fashion, a particular promoter can be programmed as to the identity of the cell and its physiological state so as to respond to hormone in a physiologically appropriate manner.

Original languageEnglish (US)
Pages (from-to)117-136
Number of pages20
JournalCurrent Topics in Microbiology and Immunology
Volume254
StatePublished - 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology (medical)
  • Immunology and Microbiology(all)
  • Microbiology

Fingerprint Dive into the research topics of 'Regulation of SMRT and N-CoR corepressor function'. Together they form a unique fingerprint.

Cite this