Disease relevance of CDC37

• These data suggest that the expression of Cdc37 may promote inappropriate proliferation and may be an important early step in the development of human prostate cancer [1].
• Two such proteins, Cdc37p and Sup45p, when overexpressed allowed partial relief of MPA toxicity, strongly suggesting that their lower amount after MPA treatment significantly contributed to the MPA effect [2].

High impact information on CDC37

• Our studies demonstrate that Cdc37 has a general role in kinome biogenesis [3].
• This degradation phenotype was suppressed when cdc37 mutant cells were grown at reduced temperatures, although this did not lead to a full restoration of kinase activity [3].
• We propose a model in which Cdc37 can function independently of Hsp90, although its ability to do so is restricted by its normally low expression levels [4].
• The protein kinase-binding domain of Cdc37 was sufficient for yeast cell viability and permitted efficient signaling through the yeast MAP kinase-signaling pathway [4].
• The yeast CDC37 gene interacts with MPS1 and is required for proper execution of spindle pole body duplication [5].

Biological context of CDC37

• The genetic interaction between KIN28 and the CDC37 cell division cycle gene suggests that a connection exists between the activity of CDK-Kin28p and cell-cycle progression [6].
• Isolation and transcriptional characterization of three genes which function at start, the controlling event of the Saccharomyces cerevisiae cell division cycle: CDC36, CDC37, and CDC39 [7].
• The quantities calculated for the three mRNA species were low, ranging from 1.5 +/- 1 copies per haploid cell for the CDC36 mRNA to 3.1 +/- 1.5 and 4.6 +/- 2 copies per haploid cell for the CDC37 and CDC39 mRNAs, respectively [7].
• The genes CDC36, CDC37, and CDC39, thought to function in the cell division control process in Saccharomyces cerevisiae, were isolated from a recombinant plasmid library prepared by partial digestion of S. cerevisiae genomic DNA with Sau3A and insertion into the S. cerevisiae-Escherichia coli shuttle vector YRp7 [7].
• Since the activation pathway for p60(v-src) and steroid hormone receptors is similar, the present study analyzed the hormone-dependent transactivation by androgen receptors and glucocorticoid receptors in yeast cells expressing a mutant version of the CDC37 gene [8].

Anatomical context of CDC37

• These data indicate that CDC37 can function as an oncogene in mice and suggests that the establishment of protein kinase pathways mediated by Cdc37-Hsp90 can be a rate-limiting event in epithelial cell transformation [9].

Associations of CDC37 with chemical compounds

• Consistent with the existence of a recently described positive feedback loop between CK2 and Cdc37, overexpression of ZDS1,2 also suppressed the temperature sensitivity, abnormal morphology, and GA sensitivity of a CK2 phosphorylation-deficient mutant of CDC37, cdc37-S14A, as well as the GA sensitivity of a cdc37-1 allele [10].
• Models for Cdc37p regulation of steroid hormone receptors are discussed [8].
• CK2 phosphorylates a conserved serine residue in the N-terminal extremity of Cdc37 in vitro and in yeast as well as mammalian cells, and this is the unique phosphorylation site of Cdc37 under normal conditions [11].

Physical interactions of CDC37

• Sti1 and Cdc37 can stabilize Hsp90 in chaperone complexes with a protein kinase [12].
• We found that, when separately expressed, the N-terminal lobe of Cdc28 interacted strongly with the C-terminal moiety of Cdc37 in a two-hybrid system [13].
• Pulse-chase analysis indicates that Cdc28 and Cak1 proteins are both destabilized when Cdc37 function is absent during but not after translation [14].

Enzymatic interactions of CDC37

• Expression of CDC37 truncation mutants that were deleted for the Hsp90-binding site stabilized v-Src and led to some folding in both sti1Delta and hsc82Delta strains [4].

Regulatory relationships of CDC37

• In addition, Cdc37 promotes the production of Cak1, but not that of Cdc28, when coexpressed in insect cells [14].
• Three components of the MAP kinase signalling system (Src, Raf, and Mek) exist in complexes with hsp90 and a 50-kDa protein that is the mammalian homolog of the yeast cell cycle control protein cdc37 [15].

Other interactions of CDC37

• Lesions in cdc28 or cdc37 did not suppress any of the ste mutations [16].
• Suppression is allele specific, and synthetic lethal interactions occur between mps1 and cdc37 alleles [5].
• The coding regions corresponding to CDC36, CDC37, and CDC39 were then identified and localized by R-loop analysis [7].
• These data suggest that Cdc37 and Sti1 have functional overlap in stabilizing Hsp90:client complexes [12].
• We report here the identification of CDC37, which encodes a putative Hsp90 co-chaperone, as a multicopy suppressor of a temperature-sensitive allele (cka2-13(ts)) of the CKA2 gene encoding the alpha' catalytic subunit of protein kinase CKII [17].

Analytical, diagnostic and therapeutic context of CDC37

• Immunoprecipitation of metabolically labeled Cdc37 from wild-type versus cka2-13 strains revealed that Cdc37 is a physiological substrate of CKII, and Ser-14 and/or Ser-17 were identified as the most likely sites of CKII phosphorylation in vivo [17].
• We propose that the CK2-Cdc37 couple can be a novel and efficient pharmacological target for cancer chemotherapy [11].
• Molecular cloning and cell cycle-dependent expression of a novel gene that is homologous to cdc37 [18].

References