HSP90AA1 is a human gene whose product cDC37** (Cell Division Cycle 37) is an Hsp90 co-chaperone that specifically facilitates the folding and maturation of protein kinases. It forms a critical complex with Hsp90 and is essential for the maturation of numerous client kinases involved in signaling pathways. Variants in HSP90AA1 have been implicated in Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
[^2]
Gene Symbol
[^3]
CDC37
Full Name
Cell Division Cycle 37
Chromosomal Location
19p13.3
NCBI Gene ID
[1111](https://www.ncbi.nlm.nih.gov/gene/1111)
OMIM
[164860](https://www.omim.org/entry/164860)
Ensembl ID
ENSG00000105401
UniProt ID
[P16234](https://www.uniprot.org/uniprot/P16234)
Protein
[CDC37-protein](/proteins/cdc37-protein)
Associated Diseases
[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis), Cancer
CDC37 (Cell Division Cycle 37) is an Hsp90 co-chaperone that specifically facilitates the folding and maturation of protein kinases. It forms a critical complex with Hsp90 and is essential for the maturation of numerous client kinases involved in signaling pathways.
CDC37 has essential co-chaperone functions:
- Kinase client loading: Specific co-chaperone for protein kinases
- Hsp90 complex formation: Bridges kinases to Hsp90
- ATPase regulation: Modulates Hsp90 ATPase activity
- Protein quality control: Ensures proper kinase folding
- Cell cycle regulation: Historic role in cell division
CDC37 interacts with:
CDC37 is implicated in AD pathogenesis:
- Regulates maturation of tau kinases (GSK3B, CDK5)
- Affects Aβ processing through kinase signaling
- Modulates APP (APP) processing
- Hsp90-CDC37 complex is a therapeutic target [1]
In PD, CDC37 plays important roles:
In ALS:
- Regulates maturation of ALS-associated kinases
- Client proteins include TBK1, OPTN
- May affect TDP-43 pathology indirectly
- Hsp90 inhibition explored as therapy [3]
CDC37 has critical roles in cancer:
- Essential for oncogenic kinase maturation
- Clients include EGFR, BCR-ABL, HER2
- Overexpressed in many cancers
- Therapeutic target
CDC37 is expressed in brain:
- Cerebral cortex: High expression in pyramidal neurons
- Hippocampus: Strong expression in all regions
- Substantia nigra: Present in dopaminergic neurons
- Cerebellum: Expressed in Purkinje cells
CDC37 expression is regulated by:
- Stress conditions
- Cell cycle factors
- Disease states
- Hsp90 inhibitors: Geldanamycin derivatives
- CDC37-specific inhibitors: Direct targeting
- Combination approaches: With kinase inhibitors
- Cancer therapy for kinase-driven tumors
- Neurodegeneration through kinase modulation
- Understanding Hsp90 biology