The Regulation Mechanism Of VD₃, 9-cis RA And Their Receptors On Transcription Of Hsp90β Gene And The Effect Of GA On Expression And Transactivity Of VDR And RXR

Hsp90 is a highly conserved, ubiquitous and abundant molecular chaperon with essential roles in stress tolerance and protein folding. In eukaryocytes, cytoplasmic Hsp90s act as specific chaperone for nuclear receptors, kinases and transcription factors. Hsp90 may be required to maintain certain nuclear receptors, such as GR, PR, ER and so on, in a potential state that functions to promote ligand binding, nuclear transportation and provide higher affinity to hormone response elements. However no direct evidence has yet been shown on the formation of stable complex between Hsp90 and VDR, TR or RXR family. Hsp90/CDC37 complex has also been shown to stabilize Cdk4 and participate indirectly in cell cycle procession. Geldanamycin (GA), known as candidate drugs for tumor chemotherapy, specifically binds to Hsp90 and inhibits at least part of its function. The phenomena aforementioned suggest that Hsp90 exert important function in cell growth.VD₃ exerts a lot of physiological functions beyond the bone mineral homeostasis realm, especially in stimulating cell differentiation, which seems to be rather contradictory to the function of Hsp90 in cell cycle procession. We are thus interested to know whether there are some regulatory interactions between them, and this study perhaps will provide some more clues for Hsp90's function on cell cycle progression.We have reported elsewhere about the important function of the first intron of hsp90P on its constitutive and heat inductive expression, in which an intronic VD₃...