Journal of Cell Science 115, e401-e401 (2002)
© 2002 The Company of Biologists Limited
N-CoR and SMRT co-repressors (p. 689)
N-CoR and SMRT are non-DNA-binding co-repressors originally shown to be
important for transcriptional repression by unliganded nuclear hormone
receptors. These co-repressors can in fact confer repression on a variety of
transcription factors, including AP-1, NF-
B, Pit-1 and STAT5. Kristen
Jepsen and Michael Rosenfeld review recent studies that have shed light on
co-repression by N-CoR and SMRT. The two proteins are components of a variety
of multiprotein complexes that contain histone deacetylases (e.g. Rpd3p or
Hda1p) — these appear to repress transcription by deacetylating lysine
residues in the N-terminal tails of histones. Regulation seems to occur at
several levels. Phosphorylation of the co-repressor can stimulate or block
association with transcription factors, depending on the kinase, and vice
versa. In addition, it can modulate the subcellular localization of the
co-repressor and its ability to form distinct co-repressor complexes. The
importance of these co-repressors for normal cell function is illustrated by
human genetic diseases such as resistance to thyroid hormone (RTH) and acute
promyelocytic leukaemia (APL), both of which inappropriately activate
N-CoR/SMRT.
Related articles in JCS:
- Biological roles and mechanistic actions of co-repressor complexes
- Kristen Jepsen and Michael G. Rosenfeld
JCS 2002 115: 689-698.
[Abstract]
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