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Summary: MINIREVIEW
Lives and Times of Nuclear Receptors
Elaine T. Alarid
Department of Physiology, University of Wisconsin-Madison, Madison, Wisconsin 53706
Down-regulation of receptor in response to ligand
was one of the earliest functional readouts of ste-
roid hormone action. The loss of total receptor
content upon stimulation, referred to initially as
receptor "processing," was carefully described
with respect to receptor nuclear transformation or
tight nuclear binding. It was these early studies
that were the first to note a correlation between
receptor turnover and induction of gene transcrip-
tion, leading to the proposal that down-regulation
of receptor was involved in mechanisms of tran-
scriptional activation. This idea has now attracted
renewed attention with the discovery that ligand-
induced "processing" in the form of proteolysis is
carried out by the 26S proteasome, a multicatalytic
enzyme whose activity is directly coupled to cell-
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