STAT1 And STAT3 In The Regulation Of Gene Expression In Hsp90¦Á

HSP90 as a important member of HSP protein family, are usually constitutively expressed in most mammalian cell types and can be further induced by heat shock and other stresses. HSP90 proteins are molecular chaperones that associated with cellar signal transduction, steroid hormone response, and cell cycle regulation, they are critical to the survival of cell in the normal and pathological condition as well as when subjected to many kind of stress. So it is very meaningful for us to study the regulatory mechanisms of the expression of human hsp90 genes. Many work have been done on studying the role of HSF and HSE in the heat shock induced expression of hsp90 genes, but much remains to be done on the relationship between other transcriptional factors and the regulation of gene expression of hsp90 genes.Mammalian HSP90 protein can be divided into two groups, HSP90αand HSP90(3 ,which are encoded by two individual genes, hsp90α and hsp90p. HSP90P can be induced by both heat shock and PHA, HSP90α can not be induced by PHA, but it is more sensitive to heat shock induction than that of the HSP90PWe have reported elsewhere that the regulatory mechanisms for the expression of hsp90a and hsp90P are different. The first intron of hsp90p is very important for its expression while the 5' flanking sequence of hsp90a plays a dominant role in the regulation of hsp90a gene expression. In our previous work we have identified a proximal heat shock element complex (HSEC) between -96/-60 that enhances hsp90α promoter expression and plays a synergistic role with the distal heat shock element. Further analysis showed that it contains two consensus binding sites for STAT that overlapping the proximal HSE. We have also found that the distal fragment from -1756 to -1463 within the 5' flanking sequence of hsp90a gene is critical for the expression, and a typical STAT1 response element(GAS) lies in the 293 bp distal fragment of the 5' flanking sequence of hsp90α gene. Based on all of the observations, we guess the STAT protein may play some role in the regulation of expression of hsp90a gene.