CDC37

CDC37

<div class="infobox infobox-gene">
<div class="infobox-header">CDC37</div>

Overview

CDC37

<div class="infobox infobox-gene">
<div class="infobox-header">CDC37</div>

Overview

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]
<div class="infobox-label">Gene Symbol</div> [@hspcdc2018]
<div class="infobox-value">CDC37</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Full Name</div>
<div class="infobox-value">Cell Division Cycle 37</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Chromosomal Location</div>
<div class="infobox-value">19p13.3</div>
</div>
<div class="infobox-row">
<div class="infobox-label">NCBI Gene ID</div>
<div class="infobox-value">[1111](https://www.ncbi.nlm.nih.gov/gene/1111)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">OMIM</div>
<div class="infobox-value">[164860](https://www.omim.org/entry/164860)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Ensembl ID</div>
<div class="infobox-value">ENSG00000105401</div>
</div>
<div class="infobox-row">
<div class="infobox-label">UniProt ID</div>
<div class="infobox-value">[P16234](https://www.uniprot.org/uniprot/P16234)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Protein</div>
<div class="infobox-value">[CDC37-protein](/proteins/cdc37-protein)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Associated Diseases</div>
<div class="infobox-value">[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis), Cancer</div>
</div>
</div>

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 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

Interaction 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 regions
• Substantia nigra: Present in dopaminergic neurons
• Cerebellum: Expressed in Purkinje cells

Regulation

CDC37 expression is regulated by:

• Stress conditions
• Cell cycle factors
• Disease states

Therapeutic Implications

Pharmacological Targeting

• Hsp90 inhibitors: Geldanamycin derivatives
• CDC37-specific inhibitors: Direct targeting
• Combination approaches: With kinase inhibitors

Research 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