Nuclear receptor coregulators
N. J. McKenna and B. W. O'Malley
Department of Molecular and Cellular Biology, Baylor
College of Medicine, Houston, TX 77030, USA
Abstract: It has been postulated that nuclear receptors (NRs)
regulate transcription via interactions with chromatin and the basal
transcription machinery at the promoters of genes. Coregulators (coactivators
or corepressors) are important in mediating these interactions and thereby
modulating positive or negative receptor activity. A large number of
putative coactivators have been isolated, several of which will be reviewed
with respect to certain "criteria" initially proposed for coactivators.
We will discuss, with reference to in vitro and in vivo experiments,
the main steps in initiation that are influenced by coactivators: (1)
initiation (e.g., SRC-1 family, CBP); (2) repetitive transcription (e.g.,
TRAPs/DRIPs); (3) RNA processing (PGC-1, etc); and (4) termination/turnover
(E6-AP, etc). A variety of enzyme functions have been implicated in
the coactivator complex including acetylase, methylase, ubiquitin ligase,
kinase, and phosphatase activities. Moreover, coactivators and corepressors
appear to exist in the steady-state cell as a series of multiprotein
complexes referred to collectively as the "coregulatorsome". Different
subcomplexes within the coregulatorsome may have different levels of
preference for individual receptors or promoters, likely contributing
to context-specific functions of NRs in target tissues.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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