Vertebrate cells synthesize two forms of the 82-to 90-kilodalton heat shock protein that are encoded by distinct gene families. In HeLa cells, both proteins (hsp89ai and hsp890) are abundant under normal growth conditions and are synthesized at increased rates in response to heat stress. Only the larger form, hsp89a, is induced by the adenovirus EIA gene product (M. C. Simon, K. Kitchener, H. T. Kao, E. Hickey, L. Weber, R. Voellmy, N. Heintz, and J. R. Nevins, Mol. Cell. Biol. 7:2884-2890. We have isolated a human hsp89a gene that shows complete sequence identity with heat-and ElA-inducible cDNA used as a hybridization probe. The 5'-flanking region contained overlapping and inverted consensus heat shock control elements that can confer heat-inducible expression on a 1-globin reporter gene. The gene contained 10 intervening sequences. The first intron was located adjacent to the translation start codon, an arrangement also found in the Drosophila hsp82 gene. The spliced mRNA sequence contained a single open reading frame encoding an 84,564-dalton polypeptide showing high homology with the hsp82 to hsp90 proteins of other organisms. The deduced hsp89a protein sequence differed from the human hsp890 sequence reported elsewhere (N. F. Rebbe, J. Ware, R. M. Bertina, P. Modrich, and D. W. Stafford (Gene 53:235-245, 1987) in at least 99 out of the 732 amino acids. Transcription of the hsp89a gene was induced by serum during normal cell growth, but expression did not appear to be restricted to a particular stage of the cell cycle. hsp89a mRNA was considerably more stable than the mRNA encoding hsp7O, which can account for the higher constitutive rate of hsp89 synthesis in unstressed cells.The 82-to 90-kilodalton (kDa) class of heat shock proteins (HSPs) have long been recognized as cytoplasmic proteins that are abundant in the absence of stress (40,42,78) and which are induced to higher levels of synthesis by heat shock. In avian and mammalian cells and tissues, these proteins (hereafter referred to as hsp89) have been found in association with several different regulatory and structural proteins. hsp89 has been shown to interact with several viral oncogene products that possess tyrosine kinase activity, including pp60src (10, 55), and the yes (46),fps (55),fes, and fgr (85) gene products. In rabbit reticulocytes, hsp89 has been identified as the 90-kDa component of highly purified preparations of the hemin-controlled translational repressor, an eIF-2ot-specific protein kinase (63). hsp89 appears to stimulate the activity of this enzyme. In avian (3,85) and calf (60) cells, hsp89 has been identified as the non-steroidbinding subunit of the estrogen receptor complex and has since been shown to be a common component of other steroid hormone receptors (33). The steroid-binding component of these receptors appears to be inactive with respect to DNA binding when complexed with hsp89 (30,58,66).
