### PSMD14 Gene Overview

**Gene Symbol**: PSMD14  
**Location**: Chromosome 2 (2p23.3)  
**Protein**: 26S proteasome non-ATPase regulatory subunit 14  

#### 1. Associated Genes

PSMD14 is associated with several other genes and proteins involved in various cellular processes, particularly those linked to proteasomal function and DNA repair mechanisms. Notable associated genes include:

- **RAD51**: Involved in homologous recombination repair.
- **TP53BP1**: Participates in non-homologous end joining (NHEJ) and recognizes DNA damage.
- **JMJD2A/KDM4A**: A histone demethylase that regulates chromatin dynamics.
- **UBC**: Ubiquitin-conjugating enzyme involved in the ubiquitin-proteasome system.
- **Ubiquitin genes (e.g., UBB, UBC)**: Various ubiquitin-related proteins important for tagging substrates for proteasomal degradation.

#### 2. Aging and Age-Related Diseases

While specific studies directly linking PSMD14 to aging are limited, its role in maintaining protein homeostasis is vital for cellular function and longevity. Increased protein misfolding and accumulation are common features of aging, and the proteasome's dysfunction can contribute to age-related diseases, such as:

- **Alzheimer's Disease**: Proteasomal impairment is linked to the accumulation of neurotoxic proteins.
- **Parkinson's Disease**: Increased oxidative stress and protein aggregation can overwhelm the proteasome, potentially implicating PSMD14 in these mechanisms.
- **Cancer**: Dysregulation of the ubiquitin-proteasome pathway, including PSMD14 activity, can lead to the accumulation of oncoproteins or loss of tumor suppressors, influencing cancer development associated with age.

#### 3. Drug Interactions

Currently, there are no specific drugs that directly target PSMD14; however, it is involved in the broader context of proteasome inhibition. Proteasome inhibitors, such as:

- **Bortezomib** (Velcade)
- **Carfilzomib**
- **Ixazomib**

These drugs are mainly used in the treatment of multiple myeloma and other hematological malignancies, indirectly influencing PSMD14's function through the modulation of the proteasome pathway.

#### 4. Pathways and Biological Processes

PSMD14 is involved in several critical biological pathways and processes, including:

- **Proteasomal Degradation**: Acts as a component of the 26S proteasome, mainly responsible for the ATP-dependent degradation of ubiquitinated proteins.
- **DNA Repair**: Involvement in non-homologous end joining (NHEJ) and homologous recombination, especially in response to double-strand breaks.
- **Cell Cycle Regulation**: Contributes to cell cycle progression by regulating protein levels that control various phases of the cycle.
- **Apoptosis**: Plays a role in regulating the degradation of pro-apoptotic and anti-apoptotic factors.
- **Proteostasis**: Maintains protein homeostasis by eliminating misfolded and damaged proteins, limiting cellular stress response.

In summary, PSMD14 is crucial for the cellular proteostasis system, the proper response to DNA damage, and overall cellular health, emphasizing its potential implications in aging and age-related diseases.