CDC37

CDC37 is a protein that is expressed in proliferative zones during embryonic development and in adult tissues, consistent with a positive role in proliferation and is required for cell division in budding yeast. CDC37 is though to play an important role in the establishment of signaling pathways controlling cell proliferation through targeting intrinsically unstable oncoprotein kinases such as Cdk-4, Raf-1, and src to the molecular chaperone Hsp90. Decreased Hsp90 expression can reduce the levels of microtubule-associated protein tau, whose overexpression may induce many diseases. CDC37 is considered as a co-chaperone that is classified to Hsp90's accessory proteins. It has been reported that suppression of Cdc37 destabilized tau, leading to its clearance, whereas cdc37 overexpression preserved tau.Cdc37 was found to co-localize with tau in neuronal cells and to physically interact with tau from human brain. Moreover, Cdc37 levels significantly increased with age.

CDC37 Related Areas

Cancer>>Cell Cycle>>Cyclin-Dependent Kinase (CDK)>>CDC37

CDC37 Alternative Names

CDC37, P50CDC37 [Homo sapiens]

Cdc37, p50, p50Cdc37 [Mus musculus]

Summaries for CDC37

Entrez Gene summary for CDC37:

The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Sacchromyces cerevisiae. This protein is a molecular chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF-1, MOK, as well as eIF2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases.

OMIM - description for CDC37:

Cyclin-dependent kinase-4 (CDK4; 123829) is a cyclin D-dependent kinase that controls progression through G1 phase of the mammalian cell cycle. To identify proteins involved in CDK4 regulation, Dai et al. (1996) analyzed CDK4 complexes from various cells by immunoprecipitation. Two proteins coimmunoprecipitated with CDK4, one with a molecular mass of 85 kD, which was found to be HSP90 (see 140571), and the other with a molecular mass of 44 kD. Dai et al. (1996) identified the second protein as the human homolog of yeast CDC37. Human CDC37 contains 378 amino acids and shares 45% and 25% amino acid identity with Drosophila and S. cerevisiae CDC37, respectively. Mutations in yeast CDC37 cause cell cycle arrest in G1 phase, and yeast CDC37 is required for the association of CDC28 and cyclin and for the activation of CDC28 (Reed, 1980). Stepanova et al. (1996) independently cloned and characterized human and mouse CDC37 by using sequences from partial cdc37-like chicken cDNA to amplify and screen various human and mouse cDNA libraries. The intracellular distribution of CDC37 was largely cytoplasmic, and the protein appeared to colocalize with cytoplasmic HSP90. CDC37 was expressed in the same tissues during development as D-type cyclins, such as proliferating zones of small intestine and stomach.

Wikipedia summary for CDC37:

Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the CDC37 gene.The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a molecular chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF1, MOK, as well as eIF-2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases.

Human CDC37 Protein General Information

 

• Protein names: Recommended name: Hsp90 co-chaperone Cdc37
• Sequence length: 378 AA.
• Sequence similarities: Belongs to the CDC37 family.
• Post-translational modification: Constitutively sumoylated by UBE2I
• Subunit structure: Forms a complex with Hsp90/HSP90AB1 and CDK6. Interacts with AR, CDK4, CDK6, EIF2AK1 and RB1
• Subcellular location: Cytoplasm

General information above from UniProt

Function for CDC37 Protein

UniProtKB:

Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity.

Genatlas:

• potential regulator of cell cycle progression
• protein kinase targeting subunit of HSP90 that binds and stabilizes CDK4 (HSPC*)
• regulator of the stress-responsive mitogen-activated protein kinase
• CDC37 plays a critical role in directing Hsp90 to its target kinases
• CDC37 is important for CDK4 stability and play a positive role in cell cycle progression
• CDC37 promotes the association of HSP90 with the protein kinase subset of client proteins to maintain their stability and signalling functions
• CDC37 essential roles for CDC37 in concert with HSP90 in maintaining oncogenic protein kinase clients
• HSP90AA2 and CDC37 mediate the maturation and stabilization of protein kinase C through a conserved PXXP motif in the C-terminal tail
• CDC37 plays potentially an essential role in regulating RYK ICD stability and therefore in RYK-mediated signal transduction
• co-chaperone that can regulate aspects of tau pathogenesis

Homology for human CDC37

• ortholog to cdc37, Danio rerio
• homolog to CDC37, Saccharomyces cerevisiae
• ortholog to Cdc37, Mus musculus
• ortholog to CDC37, Pan troglodytes
• ortholog to Cdc37, Rattus norvegicus