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Lives and Times of Nuclear Receptors

Department of Physiology, University of Wisconsin-Madison, Madison, Wisconsin 53706

Address all correspondence and requests for reprints to: Elaine T. Alarid, Ph.D., Department of Physiology, University of Wisconsin-Madison, 120 Service Memorial Institute, 1300 University Avenue, Madison, Wisconsin 53706. E-mail: alarid{at}physiology.wisc.edu.

Down-regulation of receptor in response to ligand was one of the earliest functional readouts of steroid 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 transcription, leading to the proposal that down-regulation of receptor was involved in mechanisms of transcriptional 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-cycle control, signal transduction, and importantly, transcription. Here, we review our current understanding of the mechanism and relevance of proteolysis to receptor function based on general concepts that have emerged from analyses of liganded members of the nuclear receptor family.

NURSA Molecule Pages Link:

Nuclear Receptors:   TRα  |  RARα  |  PPARα  |  PPARγ  |  VDR  |  ERα  |  GR  |  MR  |  PR  |  AR

Coregulators:   TRIP1  |  E6AP  |  UBCH7  |  BAG-1  |  BRCA1  |  SRC-1  |  NCOR  |  RPF1

Ligands:   17β-Estradiol  |  RU486

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