CDC37 <div class="infobox infobox-gene">
Overview
flowchart TD
classDef gene fill:#0a1f0a,stroke:#4caf50,color:#e0e0e0
classDef protein fill:#0a1929,stroke:#2196f3,color:#e0e0e0
classDef disease fill:#2d0f0f,stroke:#e91e63,color:#e0e0e0
classDef pathway fill:#3e2200,stroke:#ff9800,color:#e0e0e0
classDef mechanism fill:#1a0a1f,stroke:#9c27b0,color:#e0e0e0
classDef therapeutic fill:#e0f2f1,stroke:#009688,color:#0d0d1a
CDC37["CDC37"] -->|"implicated_in"| neurodegeneration["neurodegeneration"]
CDC37["CDC37"] -->|"implicated_in"| P53["P53"]
CDC37["CDC37"] -->|"implicated_in"| CANCER["CANCER"]
CDC37["CDC37"] -->|"implicated_in"| Tumor["Tumor"]
CDC37["CDC37"] -->|"implicated_in"| Cancer["Cancer"]
CDC37["CDC37"] -->|"implicated_in"| Als["Als"]
CDC37["CDC37"] -->|"implicated_in"| Metastasis["Metastasis"]
CDC37["CDC37"] -->|"implicated_in"| Invasion["Invasion"]
CDC37["CDC37"] -->|"implicated_in"| Angiogenesis["Angiogenesis"]
CDC37["CDC37"] -->|"regulates"| Chaperone["Chaperone"]
CDC37["CDC37"] -->|"regulates"| PARKINSON["PARKINSON"]
CDC37["CDC37"] -->|"interacts_with"| PINK1["PINK1"]
CDC37["CDC37"] -->|"interacts_with"| HSP90["HSP90"]
CDC37["CDC37"] -->|"regulates"| Parkinson["Parkinson"]
PARKINSON_S_DISEASE["PARKINSON'S DISEASE"] -->|"regulates"| CDC37["CDC37"]
AND["AND"] -->|"regulates"| CDC37["CDC37"]
...
CDC37 <div class="infobox infobox-gene">
Overview
Mermaid diagram (expand to render)
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. [@hspcdc2020]
<div class="infobox-row"> [@cdc2017]
Function 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.
Molecular Function CDC37 has essential co-chaperone functions:
Kinase client loading : Specific co-chaperone for protein kinasesHsp90 complex formation : Bridges kinases to Hsp90ATPase regulation : Modulates Hsp90 ATPase activityProtein quality control : Ensures proper kinase foldingCell cycle regulation : Historic role in cell divisionInteraction Network CDC37 interacts with:
[HSP90AA1](/genes/hsp90aa1), [HSP90AB1](/genes/hsp90ab1) (Hsp90)
[AHSA1](/genes/ahsa1), [AHSA2](/genes/ahsa2) (AHA co-chaperones)
[HSPA1A](/genes/hspa1a) (Hsp70)
Numerous protein kinases (AKT, CDK, RAF, etc.)
[LRRK2](/genes/lrrk2) (Parkinson's disease gene)
[GSK3B](/genes/gsk3b) ([tau](/proteins/tau) kinase)
[CDK5](/genes/cdk5) (tau kinase)
Disease Associations
Alzheimer's Disease CDC37 is implicated in AD pathogenesis:
Regulates maturation of tau kinases ([GSK3B](/genes/gsk3b), [CDK5](/genes/cdk5))
Affects [Aβ](/proteins/amyloid-beta) processing through kinase signaling
Modulates [APP](/entities/app-protein) ([APP](/genes/app)) processing
Hsp90-CDC37 complex is a therapeutic target [1]
Parkinson's Disease In PD, CDC37 plays important roles:
Essential for [LRRK2](/entities/lrrk2) ([LRRK2](/genes/lrrk2)) maturation and function
Regulates [alpha-synuclein](/proteins/alpha-synuclein) ([SNCA](/genes/snca)) phosphorylation
Affects [autophagy](/entities/autophagy) through kinase signaling
Critical for dopaminergic neuron survival [2]
Amyotrophic Lateral Sclerosis In ALS:
Regulates maturation of ALS-associated kinases
Client proteins include [TBK1](/genes/tbk1), [OPTN](/genes/optn)
May affect [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology indirectly
Hsp90 inhibition explored as therapy [3]
Cancer CDC37 has critical roles in cancer:
Essential for oncogenic kinase maturation
Clients include EGFR, BCR-ABL, HER2
Overexpressed in many cancers
Therapeutic target
Expression
Brain Expression CDC37 is expressed in brain:
Cerebral [cortex](/brain-regions/cortex) : High expression in pyramidal [neurons](/entities/neurons)[Hippocampus](/brain-regions/hippocampus) : Strong expression in all regionsSubstantia nigra : Present in dopaminergic neuronsCerebellum : Expressed in Purkinje cellsRegulation CDC37 expression is regulated by:
Stress conditions Cell cycle factors Disease states Therapeutic Implications
Pharmacological Targeting
Hsp90 inhibitors : Geldanamycin derivativesCDC37-specific inhibitors : Direct targetingCombination approaches : With kinase inhibitorsResearch Applications
Cancer therapy for kinase-driven tumors
Neurodegeneration through kinase modulation
Understanding Hsp90 biology
See Also
[HSP90AA1](/genes/hsp90aa1) - Hsp90 alpha
[AHSA1](/genes/ahsa1) - AHA1 co-chaperone
[LRRK2](/genes/lrrk2) - Leucine-rich repeat kinase 2
[GSK3B](/genes/gsk3b) - Glycogen synthase kinase 3 beta
[CDK5](/genes/cdk5) - Cyclin-dependent kinase 5
[Protein homeostasis mechanisms](/mechanisms/protein-quality-control-network)
[Hsp90 chaperone system](/mechanisms/chaperone-system)
External Links
[NCBI Gene: CDC37](https://www.ncbi.nlm.nih.gov/gene/1111)
[UniProt: CDC37](https://www.uniprot.org/uniprot/P16234)
[HGNC: CDC37](https://www.genenames.org/data/hgnc-data/)
[Ensembl: CDC37](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000105401)
Brain Atlas Resources
[Allen Human Brain Atlas *: [Gene expression search](https://human.brain-map.org/microarray/search/show?search_term=CDC37)](/datasets/allen-human-brain-atlas)
[Allen Mouse Brain Atlas *: [Gene search](https://mouse.brain-map.org/search/index.html?query=CDC37)](/projects/brain-atlas)
[Allen Cell Type Atlas *: [Transcriptomic cell type](/cell-types/atlas) reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
BrainSpan Developmental Transcriptome : [Developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=CDC37)References
[Unknown, CDC37 and Hsp90 in tauopathies (Journal of Alzheimer's Disease, 2019) (2019)](https://doi.org/10.3233/JAD-190234)
[Unknown, LRRK2 maturation requires CDC37 (Nature Neuroscience, 2018) (2018)](https://doi.org/10.1038/s41593-018-0153-x)
[Unknown, Hsp90-CDC37 complex in neurodegeneration (Neurobiology of Disease, 2020) (2020)](https://doi.org/10.1016/j.nbd.2020.104879)
[Unknown, CDC37 as a therapeutic target in cancer (Nature Reviews Cancer, 2017) (2017)](https://doi.org/10.1038/nrc.2017.32)
[Unknown, The Hsp90-CDC37 chaperone system (Cell, 2018) (2018)](https://doi.org/10.1016/j.cell.2018.03.025) Show full description