Genetic and Molecular Analysis of Division Control in Yeast

Reed, Steven I.; Lopes, Maíza Alves; Ferguson, Jill; Hadwiger, Jeffrey A.; Ho, Jeong-Yau; Horwitz, Rick; Jones, C. E.; Lörincz, Attila T.; Mendenhall, Michael J.; Peterson, Thomas; Richardson, Stephanie L.; Wittenberg, Curt

doi:10.1101/sqb.1985.050.01.076

Cited by 24 publications

(11 citation statements)

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“…comm. ), kin28 (Valey et al 1995), pp60v-s'c (Boschelli 1993Xu and Lindquist 1993), and cdc28 (Reed et al 1985). In addition, Hsp90 homologs interact genetically with wee1 + in fission yeast (Aligue et al 1994), with pp6OV-"'" in budding yeast (Nathan and Lindquist 1995), and with torso and sevenless tyrosine kinases in Drosophila (Doyle andBishop 1993 Cutforth andRubin 1994).…”

Section: Cdc37/hsp90 As a General Protein Kinase Chaperonementioning

confidence: 99%

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Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4.

Stepanova¹,

Leng²,

Parker³

et al. 1996

Genes Dev.

460

450

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CDC37, an essential gene in Saccharomyces cerevisiae, interacts genetically with multiple protein kinases and is required for production of Cdc28p/cyclin complexes through an unknown mechanism. We have identified mammalian p50Cdc37 as a protein kinase-targeting subunit of the molecular chaperone Hsp90. Previously, p50 was observed in complexes with pp60v-src and Raf-1, but its identity and function have remained elusive. In mouse fibroblasts, a primary target of Cdc37 is Cdk4. This kinase is activated by D-type cyclins and functions in passage through G1. In insect cells, Cdc37 is sufficient to target Hsp90 to Cdk4 and both in vitro and in vivo, Cdc37/Hsp90 associates preferentially with the fraction of Cdk4 not bound to D-type cyclins. Cdc37 is coexpressed with cyclin Dl in cells undergoing programmed proliferation in vivo, consistent with a positive role in cell cycle progression. Pharmacological inactivation of Cdc37/Hsp90 function decreases the half-life of newly synthesized Cdk4, indicating a role for Cdc37/Hsp90 in Cdk4 stabilization. This study suggests a general role for p50Cdc37 in signaling pathways dependent on intrinsically unstable protein kinases and reveals a previously unrecognized chaperone-dependent step in the production of Cdk4/cyclin D complexes.

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Section: Cdc37/hsp90 As a General Protein Kinase Chaperonementioning

confidence: 99%

“…CDC37 was identified as a START mutant (Reed 1980;Reed et al 1985;Ferguson et al 1986) but is required at other points in the cell cycle as well (Gerber et al 1995). In cdc37-1 mutant strains at the restrictive temperature, Cdc28p and cyclin proteins are present but not assembled (Gerber et al 1995).…”

mentioning

confidence: 99%

Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4.

Stepanova¹,

Leng²,

Parker³

et al. 1996

Genes Dev.

460

450

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“…CDC37 was identified in a screen for synthetic lethality with a Ts allele of K1N28, which encodes a kinase associated with the general transcription factor TFIIH (Feaver et al, 1994;Valay et al, 1995). Both Cdc37p and Hsp9O have been implicated in the function of the sevenless protein tyrosine kinase in Drosophila (Cutforth and Rubin, 1994), whereas, in both yeast and Drosophila, genetic interaction between Cdc37p and the cyclin-dependent kinase p34CIc28 (in yeast) and p34C c2 (in Drosophila) has been reported (Reed et al, 1985;Cutforth and Rubin, 1994). This genetic interaction probably reflects the requirement of Cdc37p for association of p34CDC28 kinase with cyclins (Gerber et al, 1995).…”

Section: Cdc37 In Normal Cellular Regulationmentioning

confidence: 99%

CDC37 is required for p60v-src activity in yeast.

Dey

Lightbody

Boschelli

1996

MBoC

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Mutations in genes encoding the molecular chaperones Hsp9O and Ydjlp suppress the toxicity of the protein tyrosine kinase p6Ov-src in yeast by reducing its levels or its kinase activity. We describe isolation and characterization of novel p60v-src-resistant, temperature-sensitive cdc37 mutants, cdc37-34 and cdc37-17, which produce less p6Ov-src than the parental wild-type strain at 23°C. However, p6Ov-src levels are not low enough to account for the resistance of these strains. Asynchronously growing cdc37-34 and cdc37-17 mutants arrest in G1 and G2/M when shifted from permissive temperatures (23°C) to the restrictive temperature (370C), but hydroxyurea-synchronized cdc37-34 and cdc37-17 mutants arrest in G2/M when released from the hydroxyurea block and shifted from 23 to 37°C. The previously described temperature-sensitive cdc37-1 mutant is p6Ov-src_ sensitive and produces wild-type amounts of p6ov-src at permissive temperatures but becomes p60v-src-resistant at its restrictive temperature, 38°C. In all three cdc37 mutants, inactivation of Cdc37p by incubation at 38°C reduces p60v-src-dependent tyrosine phosphorylation of yeast proteins to low or undetectable levels. Also, p6Ov-src levels are enriched in urea-solubilized extracts and depleted in detergent-solubilized extracts of all three cdc37 mutants prepared from cells incubated at the restrictive temperature. These results suggest that Cdc37p is required for maintenance of p6ov-src in a soluble, biologically active form. INTRODUCTIONThe 60-kDa oncogenic protein tyrosine kinase of Rous

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“…In yeast, cdc37 mutations cause synthetic lethality (as defined by Kaelin (56)) in combination with thermosensitive cdc28 or kin28 mutations (12,13). The mammalian homolog of Cdc37, also referred to as p50 cdc37 , was first identified within a complex consisting of the Rous sarcoma virus encoded oncogene pp60…”

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confidence: 99%