### PSME3 Gene Overview

**Gene Symbol**: PSME3  
**Location**: Human chromosome 14q31.3  
**Function**: The PSME3 gene encodes for the gamma subunit of the 11S regulator (or PA28-gamma) associated with the proteasome. This subunit plays a vital role in antigen processing and the regulation of the proteasome's enzymatic activity, influencing various cellular processes including apoptosis, cell cycle regulation, and tumor suppression.

### 1. Associated Genes

The PSME3 gene is known to interact with several other genes and proteins, including but not limited to:

- **TP53**: The p53 tumor suppressor protein, whose degradation is facilitated by PSME3 through its interaction with MDM2.
- **MDM2**: The oncoprotein that helps regulate p53 via ubiquitination.
- **CCAR2 (Cell Cycle and Apoptosis Regulator 2)**: A potential modulator of PSME3 activity in relation to SIRT1 inhibition.

Additionally, PSME3 may indirectly affect the expression and activity of genes involved in:

- Cell cycle regulation (e.g., CDKs).
- Apoptosis (e.g., BAX, BCL2).
- DNA repair mechanisms (e.g., CHEK2).

### 2. Aging and Age-Related Diseases

While direct associations to aging-related processes are still being researched, certain implications exist regarding PSME3:

- **Tumorigenesis**: The role of PSME3 in the degradation of p53 suggests a potential link to cancer, which is often described as age-related due to the accumulation of mutations and altered signaling pathways over time.
- **Cellular Senescence**: Affected regulation of p53 is crucial for maintaining cellular homeostasis, and alterations in this regulation might influence senescence pathways.
- **Neurodegeneration**: Dysregulation of proteasomal activity has been implicated in the pathology of neurodegenerative diseases, where p53 can modulate neuronal cell fate in response to DNA damage, suggesting that PSME3 might be indirectly involved.

### 3. Known Drug Interactions

Drugs and drug classes that may interact with PSME3 include:

- **Proteasome inhibitors**: Such as Bortezomib (Velcade) and Carfilzomib, which are used in cancer therapies. These drugs could potentially alter proteasomal functions in which PSME3 is involved.
- **MDM2 antagonists**: Such as Nutlin-3, which inhibit MDM2 activity and indirectly may influence the dynamics between p53 and PSME3.
- **SIRT1 inhibitors**: Any drugs targeting SIRT1 directly might affect pathways involving PSME3 related to p53 regulation.

### 4. Pathways and Biological Processes

PSME3 is involved in several key pathways and biological processes, including:

- **Proteasome-mediated degradation**: Crucial for the regulation of protein turnover, particularly of ubiquitin-tagged substrates.
- **Antigen processing and presentation**: Particularly in the MHC class I pathway, highlighting PSME3's role in immune responses.
- **Regulation of apoptosis**: Through the modulation of p53 degradation, influencing cell survival and response to DNA damage.
- **Cell cycle regulation**: Involvement with CCAR2 and CHEK2 suggests roles in monitoring cell cycle progression and stress responses.

### Summary

The PSME3 gene plays a critical role in the proteasomal pathway as part of the 11S regulator, significantly influencing protein degradation, cell cycle regulation, and apoptosis through its interactions with key proteins like p53 and MDM2. While still an area of ongoing research, its involvement in age-related diseases and cellular senescence provides an intriguing avenue for future investigations.