tailieunhanh - Báo cáo khoa học: Cdc37 maintains cellular viability in Schizosaccharomyces pombe independently of interactions with heat-shock protein 90

Cdc37 is a molecular chaperone that interacts with a range of clients and co-chaperones, forming various high molecular mass complexes. Cdc37 sequence homology among species is low. High homology between yeast and metazoan proteins is restricted to the extreme N-terminal region, which is known to bind clients that are predominantly protein kinases. | ềFEBS Journal Cdc37 maintains cellular viability in Schizosaccharomyces pombe independently of interactions with heat-shock protein 90 Emma L. Turnbull Ina V. Martin and Peter A. Fantes Institute of Cell Biology Schoolof BiologicalSciences University of Edinburgh UK Keywords Cdc37 fission yeast heat-shock protein 90 Hsp90 molecular chaperone pombe Correspondence P. A. Fantes Institute of CellBiology Schoolof BiologicalSciences Mayfield Road University of Edinburgh Edinburgh EH9 3JR UK Fax 44 131 651 3331 Tel 44 131 650 5669 E-mail Present address Institute of Physiology RWTH Aachen Uniklinikum Pauwelsstr. 30 52074 Aachen Germany Received 11 May 2005 revised 17 June 2005 accepted 20 June 2005 doi Cdc37 is a molecular chaperone that interacts with a range of clients and co-chaperones forming various high molecular mass complexes. Cdc37 sequence homology among species is low. High homology between yeast and metazoan proteins is restricted to the extreme N-terminal region which is known to bind clients that are predominantly protein kinases. We show that despite the low homology both Saccharomyces cerevisiae and human Cdc37 are able to substitute for the Schizosaccharomyces pombe protein in a strain deleted for the endogenous cdc37 gene. Expression of a construct consisting of only the N-terminal domain of S. pombe Cdc37 lacking the postulated heat-shock protein Hsp 90-binding and homodimerization domains can also sustain cellular viability indicating that Cdc37 dimerization and interactions with the cochaperone Hsp90 may not be essential for Cdc37 function in S. pombe. Biochemical investigations showed that a small proportion of total cellular Cdc37 occurs in a high molecular mass complex that also contains Hsp90. These data indicate that the N-terminal domain of Cdc37 carries out essential functions independently of the Hsp90-binding domain and dimerization of the chaperone itself. Cdc37 is a molecular chaperone that