The Schizosaccharomyces pombe Cdc7 Protein Kinase Required for Septum Formation Is a Client Protein of Cdc37

Abstract

Cdc37 is an essential molecular chaperone found in fungi and metazoa whose main specificity is for certain protein kinases. Cdc37 can act as an Hsp90 cochaperone or alone; in yeasts, the interaction with Hsp90 is weak and appears not to be essential for Cdc37 function. Numerous genetic interactions between Cdc37 and likely client proteins have been observed in yeasts, but biochemical confirmation has been reported in only a few cases. We and others have generated and characterized temperature-sensitive cdc37 alleles in S. pombe and have used them to investigate the cellular roles of Cdc37: previous work has shown that mitotic Cdc2 is a major client. In this paper, we describe a screen for mutations synthetically lethal with a cdc37ts mutant with the aim of identifying genes encoding further client proteins of Cdc37. Ten such strains were isolated, and genomic libraries were screened for rescuing plasmids. In one case, a truncated cdc7 gene was identified. Further experiments showed that the mutation in this strain was indeed in cdc7. Cdc7 is a protein kinase required for septum initiation, and we show that its kinase activity is greatly reduced when Cdc37 function is impaired. Cdc7 normally locates to the spindle pole body during mitosis, and this appears to be unaffected in the cdc37ts mutant. Other evidence suggests that, in addition to mitosis and septum initiation, Cdc37 may also be required for septum cleavage.

Genomic and Proteomic Analyses of the Fungus Arthrobotrys oligospora Provide Insights into Nematode-Trap Formation

“…In this study, the expression levels of Cdc37 (a molecular chaperone, AOL_s00043g594) and Mih1 (a phosphatases, AOL_s00176g31) ( Table S7 ) were up-regulated during the formation of traps (10 h). In S. cerevisiae and Schizosaccharomyces pombe , Cdc37 is required for maintaining the protein level of a cyclin-dependent kinase Cdc28, a key enzyme for regulating the G1-S and the G2-M phase transitions [36] . Similarly, Mih1 promotes cell entry into mitosis by removing the inhibitory phosphorylation placed on Cdk1 by Wee1 in S. cerevisiae [37] .…”

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

“…Sti1p binds as a dimer to the HSP90 dimer and is an inhibitor of ATPase activity (942,943). CDC37 functions in a similar manner, but it recruits protein kinases as client proteins and inhibits ATPase activity (944,945). The mammalian CHIP (carboxyl terminus of HSC70-interacting protein) is an E3 ubiquitin ligase, which interacts by its TPR domain with HSP70 and HSP90 and exerts its ubiquitylating activity by the U-box domain (946)(947)(948).…”