CDK4 Gene

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CDK4 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CDK4 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CDK4</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Cyclin-Dependent Kinase 4</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>12q14.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1019</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000136492</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P11802</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>CDK4, PSK-J3</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Approval</td>
</tr>
<tr>
<td class="label">Palbociclib</td>
<td>FDA approved</td>
</tr>
<tr>
<td class="label">Ribociclib</td>
<td>FDA approved</td>
</tr>
<tr>
<td class="label">Abemaciclib</td>
<td>FDA approved</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/ataxia" style="color:#ef9a9a">Ataxia</a>, <a href="/wiki/autism" style="color:#ef9a9a">Autism</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">321 edges</a></td>
</tr>
</table>

...

CDK4 Gene

Introduction

Cdk4 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Pathway Diagram

Mermaid diagram (expand to render)

Overview

CDK4 encodes cyclin-dependent kinase 4, a serine/threonine kinase that forms a complex with D-type cyclins (CYCLIN D1, D2, D3) to drive cell cycle progression from G1 to S phase. CDK4 is a key regulator of the cell cycle and is frequently dysregulated in cancer. In the nervous system, CDK4 plays important roles in neurogenesis, synaptic plasticity, and cell cycle control. Aberrant CDK4 activation is implicated in neuronal death in neurodegenerative diseases [@cdk2007][@cell2013].

Gene Information

Gene Structure

CDK4 spans ~4.5 kb:

Exons: 8 coding exons
Transcript: ~2.2 kb mRNA
Protein: 303 amino acids, ~34 kDa

Normal Function

Cell Cycle Control

CDK4 regulates:

G1/S transition — Phosphorylates RB
E2F release — Enables S-phase genes
Cyclin D binding — Required for activity
Thr172 phosphorylation — Activation

Cell Cycle Checkpoints

CDK4 in:

Restriction point — G1 checkpoint
DNA damage response — Can be inhibited
Contact inhibition — Growth factor dependent

Neuronal Functions

In neurons:

Cell cycle exit — Post-mitotic neurons exit cycle
Synaptic plasticity — Regulates synaptic proteins
DNA repair — Cell cycle genes in repair

Role in Neurodegeneration

Alzheimer's Disease

CDK4 in AD:

Cell cycle re-entry — [Neurons](/entities/neurons) re-enter cycle inappropriately
[Tau](/proteins/tau) phosphorylation — CDK4 can phosphorylate tau
Neuronal death — Cycle activation leads to death
Therapeutic target — CDK4 inhibitors

Parkinson's Disease

Cell cycle activation — Seen in PD brains
Dopaminergic loss — CDK4 in neuron death

Stroke

Ischemic injury — CDK4 activated after stroke

Key Publications

PMID: 8340146(https://pubmed.ncbi.nlm.nih.gov/8340146/) — Discovery of CDK4

PMID: 10625657(https://pubmed.ncbi.nlm.nih.gov/10625657/) — CDK4 structure and function

PMID: 11025718(https://pubmed.ncbi.nlm.nih.gov/11025718/) — CDK4 in cell cycle

PMID: 21479819(https://pubmed.ncbi.nlm.nih.gov/21479819/) — CDK4 in neurodegeneration

Background

The study of Cdk4 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
[Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

Cell Cycle Control

CDK4 in G1 Phase

CDK4 is the key G1 kinase:

[G1 progression*: Essential for G1/S transition](/genes/ran)
[Retinoblastoma phosphorylation*: Releases E2F](/genes/ret)
[Cyclin D partnership*: CDK](/genes/ar)4-cyclin D complexes
Growth factor signaling: Links external signals to cell cycle

Regulation

Cyclin D1-3: Three cyclin D isoforms
INK4 inhibitors: p16INK4a, p15INK4b, p18INK4c, p19INK4d
CIP/KIP inhibitors: p21CIP1, p27KIP1
Phosphorylation: Inhibitory (T172) and activating sites

Neurobiology

Neuronal Expression

CDK4 in the nervous system:

Developmental expression: High in neural progenitors
Adult brain: Low baseline, inducible
Activity-dependent: Regulated by neuronal activity
Glia: Present in [astrocytes](/entities/astrocytes) and [microglia](/entities/microglia)

Alzheimer's Disease

CDK4 in AD:

Neuronal cell cycle: Pathological re-entry
Amyloid response: [Aβ](/proteins/amyloid-beta) activates CDK4
Tau kinase: Phosphorylates [tau protein](/proteins/tau)
Synaptic plasticity: Role in memory formation

Parkinson's Disease

Dopaminergic neurons: Cell cycle alterations
[α-Synuclein](/proteins/alpha-synuclein) phosphorylation: Potential substrate
Mitochondrial dysfunction: Links to energy metabolism
Neuroinflammation: Cyclin D in glial activation

Stroke and Brain Injury

Ischemic stroke: CDK4 activation after injury
Neurogenesis: Role in neural stem cells
Reparative processes: Tissue remodeling

Animal Models

Knockout Studies

Cdk4 knockout mice:

Viable: Survive to adulthood
Growth retardation: Smaller body size
Diabetes: β-cell proliferation defects
Neural phenotypes: Some developmental defects

Transgenic Models

Neuronal CDK4: Neuronal-specific expression
p16INK4a models: Tumor suppressor studies
AD models: [APP](/entities/app-protein)/PS1 crossed with CDK4

Therapeutic Targeting

CDK4/6 Inhibitors

CNS Applications

Brain cancer: Glioma therapy potential
Neurodegeneration: Protective effects
Challenges: [Blood-brain barrier](/entities/blood-brain-barrier) penetration
Combination therapy: With other agents

Summary

CDK4 links growth factor signaling to cell cycle progression. In the brain, dysregulated CDK4 activity contributes to neuronal dysfunction in AD and PD. CDK4/6 inhibitors approved for cancer may have therapeutic potential in neurodegeneration.

References

[Unknown, CDK4 in Alzheimer's disease pathogenesis (2007) (2007)](https://pubmed.ncbi.nlm.nih.gov/17634367/)

[Unknown, Cell cycle kinases in neurodegeneration (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23616150/)

[Unknown, CDK4/6 inhibitors for AD therapy (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30762218/)

[Unknown, Tau phosphorylation by CDK4 (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/22037012/)

Pathway Diagram

The following diagram shows the key molecular relationships involving CDK4 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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CDK4 Gene

CDK4 Gene

Introduction

CDK4 Gene

Introduction

Pathway Diagram

Overview

Gene Information

Gene Structure

Normal Function

Cell Cycle Control

Cell Cycle Checkpoints

Neuronal Functions

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Stroke

Key Publications

See Also

Background

External Links

Cell Cycle Control

CDK4 in G1 Phase

Regulation

Neurobiology

Neuronal Expression

Alzheimer's Disease

Parkinson's Disease

Stroke and Brain Injury

Animal Models

Knockout Studies

Transgenic Models

Therapeutic Targeting

CDK4/6 Inhibitors

CNS Applications

Summary

References

Pathway Diagram