CCND1 Protein (Cyclin D1)

CCND1 Protein (Cyclin D1)

Overview

Cyclin D1 (CCND1) is a regulatory subunit of cyclin-dependent kinases (CDKs) that controls the G1/S phase transition of the cell cycle. While primarily studied in cancer biology, Cyclin D1 has emerged as an important player in neuronal cell cycle dysregulation observed in neurodegenerative diseases. [@cell2019]

<div class="infobox infobox-protein"> [@cyclin2020]
<div class="infobox-header">Cyclin D1 (CCND1)</div> [@amyloidbeta2021]
<table> [@cyclin2018]
<tr><th>Gene</th><td>[CCND1](/genes/ccnd1)</td></tr> [@cyclin2022]
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/P24385" target="_blank">P24385</a></td></tr> [@cell2020]
<tr><th>PDB ID</th><td><a href="https://www.ebi.ac.uk/pdbe/3MRD" target="_blank">3MRD</a>, <a href="https://www.ebi.ac.uk/pdbe/5EX4" target="_blank">5EX4</a></td></tr> [@cyclin2019]
<tr><th>Protein Family</th><td>Cyclin family</td></tr>
<tr><th>Molecular Weight</th><td>~34 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Nucleus, Cytoplasm</td></tr>
<tr><th>Expression</th><td>Proliferating cells; low in mature [neurons](/entities/neurons)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2 edges</a></td>
</tr>
</table>
</div>

Structure

Cyclin D1 possesses the canonical cyclin fold structure:

CCND1 Protein (Cyclin D1)

Overview

Cyclin D1 (CCND1) is a regulatory subunit of cyclin-dependent kinases (CDKs) that controls the G1/S phase transition of the cell cycle. While primarily studied in cancer biology, Cyclin D1 has emerged as an important player in neuronal cell cycle dysregulation observed in neurodegenerative diseases. [@cell2019]

<div class="infobox infobox-protein"> [@cyclin2020]
<div class="infobox-header">Cyclin D1 (CCND1)</div> [@amyloidbeta2021]
<table> [@cyclin2018]
<tr><th>Gene</th><td>[CCND1](/genes/ccnd1)</td></tr> [@cyclin2022]
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/P24385" target="_blank">P24385</a></td></tr> [@cell2020]
<tr><th>PDB ID</th><td><a href="https://www.ebi.ac.uk/pdbe/3MRD" target="_blank">3MRD</a>, <a href="https://www.ebi.ac.uk/pdbe/5EX4" target="_blank">5EX4</a></td></tr> [@cyclin2019]
<tr><th>Protein Family</th><td>Cyclin family</td></tr>
<tr><th>Molecular Weight</th><td>~34 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Nucleus, Cytoplasm</td></tr>
<tr><th>Expression</th><td>Proliferating cells; low in mature [neurons](/entities/neurons)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2 edges</a></td>
</tr>
</table>
</div>

Structure

Cyclin D1 possesses the canonical cyclin fold structure:

• N-terminal region: Required for CDK binding and activation
• Cyclin box domain: Conserved 100 amino acid sequence that binds CDKs (especially CDK4 and CDK6)
• C-terminal region: Contains degron sequences for protein turnover
• PEST sequences: Rich in proline, glutamic acid, serine, threonine

Normal Function

In the normal nervous system:

In mature neurons, CCND1 expression is typically very low as these cells are post-mitotic.

Role in Neurodegeneration

Alzheimer's Disease

In AD, Cyclin D1 dysregulation is prominent:

• Re-expression in AD neurons: Aberrant cell cycle entry in vulnerable neurons [1]
• [Tau](/proteins/tau) phosphorylation: Interaction with CDK4/6 promotes tau pathology [2]
• [Aβ](/proteins/amyloid-beta)-induced toxicity: Contributes to neuronal dysfunction [3]
• Correlates with neurofibrillary tangle burden [4]

Parkinson's Disease

In PD:

• Elevated in dopaminergic neurons
• Associated with [alpha-synuclein](/proteins/alpha-synuclein) pathology
• Contributes to mitochondrial dysfunction
• May drive neuronal senescence [5]

Amyotrophic Lateral Sclerosis

In ALS:

• Dysregulated in motor neurons
• Associated with [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology
• Contributes to cell cycle re-entry
• May exacerbate proteostasis failure [6]

Huntington's Disease

In HD:

• Increased Cyclin D1 in medium spiny neurons
• Contributes to transcriptional dysregulation
• May interact with mutant [huntingtin](/proteins/huntingtin)
• Linked to striatal neuron vulnerability [7]

Therapeutic Targeting

Strategies

• CDK4/6 inhibitors (e.g., palbociclib): Indirectly modulate Cyclin D1 activity
• Gene expression modulators: Downregulate CCND1 transcription
• Cell cycle normalization: Restore post-mitotic state in neurons

Clinical Status

• CDK4/6 inhibitors approved for cancer, being repurposed
• Preclinical studies show promise in neurodegeneration models
• Clinical trials for AD underway

Protein Interactions

| Partner | Interaction Type | Function |
|---------|------------------|----------|
| CDK4 | Binding | Kinase complex formation |
| CDK6 | Binding | Kinase complex formation |
| p21/CDKN1A | Regulation | CDK inhibition |
| p27/CDKN1B | Regulation | CDK inhibition |
| RB1 | Phosphorylation | Cell cycle progression |
| RbAp46/48 | Chromatin remodeling | Transcriptional control |

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References