BAG-1 family of cochaperones in the modulation of nuclear receptor action.
BAG-1 is a family of cochaperones consisting of at least four polypeptides BAG-1L, BAG-1M/RAP46, BAG-1 and p29. These proteins are translated from the same mRNA at alternative translation initiation sites. They possess conserved carboxy-terminal sequences which enable them to bind and inhibit the action of the molecular chaperone Hsp70/Hsc70. BAG-1 was the first member in the family of the BAG-1 proteins to be isolated. It was identified as an anti-apoptotic protein because of its ability to bind and augment the activity of the anti-death protein, Bcl-2. Since then other BAG-1 proteins have been identified and shown to interact with several cellular factors including nuclear receptors. Recent findings show that the effect of the BAG-1 proteins on nuclear receptors ranges from inhibition to enhancement of the transactivation functions of the receptors. Available data on the negative regulation of glucocorticoid receptor (GR) action by the BAG-1 proteins identify two modes of action: inhibition of the hormone binding activity of the GR and a more direct nuclear action at the level of regulation of the transactivation function of the receptor. In the latter case, the BAG-1 proteins repress DNA binding by the GR in a process that requires prior binding of Hsp70/Hsc70 to the receptor. Positive regulatory action of the BAG-1 proteins on nuclear receptors has also been reported which may involve yet other mechanisms. This review puts together recent findings on the action the BAG-1 proteins and presents them as a novel group of regulators of action of nuclear receptor.
Cato
A C
AC
Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, PO Box 3640, D-76021, Karlsruhe, Germany. andrew.cato@itg.fzk.de
Mink
S
S
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors