### UBE2D3 Gene Overview

**Gene Symbol**: UBE2D3  
**Gene Type**: Protein coding  
**Chromosomal Location**: Human: 14q24.3

The UBE2D3 gene encodes a member of the ubiquitin-conjugating enzyme family, which plays a pivotal role in the ubiquitin-proteasome pathway, a crucial mechanism for protein degradation and various cellular processes including cell cycle regulation, signal transduction, and DNA repair.

### Key Functions

UBE2D3 mediates the ubiquitination process, which involves:
- Accepting ubiquitin from ubiquitin-activating enzymes (E1) and covalently attaching it to target proteins.
- It is involved in the ubiquitination of several key proteins, notably:
  - **p53/TP53**: A tumor suppressor protein, facilitating its degradation.
  - **NFKBIA**: Involved in signaling pathways regulating immune and inflammatory responses.
  - **PCNA**: Plays an essential role in DNA replication and repair.
  - **EGFR**: A critical receptor involved in cell signaling, particularly in proliferation and survival pathways.

### Gene Associations

Other genes associated with UBE2D3's activity or processes include:

- **MDM2** and **TOPORS**: Both are E3 ligases involved in the ubiquitination of p53.
- **CDC34**: An E2 enzyme that cooperates with UBE2D3 for the elongation of ubiquitin chains.
- **BRCA1** and **BARD1**: These E3 complex partners for UBE2D3 participate in DNA repair mechanisms.
- **RNF8**: Works with UBE2D3 in monoubiquitinating PCNA.
- **CBL**: Involved in the polyubiquitination of EGFR.
- **RIGI**: Related to viral RNA and interferon signaling.
- **ZNF598**: Involved in ribosome collision response.

### Association with Aging and Age-Related Diseases

- **DNA Repair**: UBE2D3's role in DNA damage repair via PCNA and BRCA1/BARD1 links it to aging, where DNA damage accumulation is observed.
- **Cancer**: Because UBE2D3 is involved in the degradation of tumor suppressors like p53, dysregulation can contribute to oncogenesis and tumor progression, often observed in age-related cancer incidence.
- **Neurodegenerative Diseases**: Ubiquitination processes are implicated in neurodegenerative conditions, and alteration in UBE2D3 functions may be relevant to diseases such as Alzheimer’s or Parkinson's.

### Drug Interactions

While specific drug interactions directly with UBE2D3 haven't been widely detailed, its role in ubiquitination suggests potential indirect interactions with:

- **Proteasome inhibitors** (such as Bortezomib): Drugs that inhibit protein degradation could impact UBE2D3 functions.
- **Chemotherapeutic agents** that target cell cycle regulation and apoptosis may manipulate pathways involving UBE2D3.

### Pathways and Biological Processes

UBE2D3 is involved in various cellular pathways and biological processes, such as:

1. **Ubiquitin-Proteasome Pathway**: Essential for the regulated degradation of proteins.
2. **DNA Damage Repair**: Involvement in various stages of DNA repair mechanisms including nucleotide-excision repair and double-strand break repair.
3. **Cell Cycle Regulation**: Through its effects on key proteins like p53, influencing cell cycle arrest and apoptosis.
4. **Immune Response**: Participation in pathways modulating immune signaling, especially via NFKBIA and RIGI interactions.
5. **Signal Transduction**: In the context of EGFR, influencing cell proliferation and differentiation signals.

### Summary

UBE2D3 is a critical component of the ubiquitination process, directly involved in regulating essential cellular functions related to cancer, DNA repair, and immune responses. Its interactions and regulatory activities make it a significant focus of research relating to aging and age-associated pathologies, as well as for potential therapeutic interventions.