### USP37 Gene Overview

**Gene Symbol:** USP37  
**Function:** The USP37 gene encodes a deubiquitinating enzyme which plays a crucial role in regulating the cell cycle, particularly the G1/S transition. This is achieved through its deubiquitination activities on cyclins A1 and A2, thus influencing cell cycle progression and promoting S phase entry.

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### 1. Associated Genes
In addition to cyclins A1 (CCNA1) and A2 (CCNA2), USP37 interacts with several other genes and proteins involved in the cell cycle and DNA regulation processes, including:

- **CDT1 (Chromatin Licensing and DNA Replication Factor 1):** A licensing factor for DNA replication that USP37 stabilizes.
- **APC/C (Anaphase-Promoting Complex/Cyclosome):** A multi-subunit E3 ubiquitin ligase complex that is antagonized by USP37 through deubiquitination of its substrates.

Additional genes linked to USP37 could include other ubiquitin-conjugating enzymes or key regulators of the cell cycle, although specific gene associations may vary based on cellular context and conditions.

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### 2. Aging and Age-Related Diseases
While specific studies on USP37 and aging are limited, the cell cycle dysregulation and the improper management of DNA replication can be linked to age-related cellular functions, such as: 

- **Cancer:** Dysregulation of the cell cycle due to alterations in deubiquitinating enzymes like USP37 can contribute to tumorigenesis.
- **Neurodegenerative Disorders:** Impaired cell cycle regulation and DNA replication have been linked with neurodegeneration.
- **Cellular Senescence:** USP37's role in maintaining cyclin levels may influence cellular senescence, which is a critical factor in aging and age-related diseases.

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### 3. Drug Interactions
Specific drugs or drug classes that might modulate the activity of USP37 include:

- **Inhibitors of the proteasome (e.g., Bortezomib):** While these do not target USP37 directly, they may influence the cellular ubiquitination landscape, which in turn can affect USP37's functionality.
- **Kinase inhibitors:** Since phosphorylation at Ser-628 enhances USP37 activity, certain kinase inhibitors could indirectly influence USP37 activity by modulating the phosphorylation state of the enzyme.

Further drug interactions may emerge as specific USP37 inhibitors or modulators are developed, though these are currently under research.

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### 4. Pathways and Biological Processes 
USP37 is involved in a variety of cellular pathways and biological processes, including:

- **Cell Cycle Regulation:** Particularly during the G1/S transition, through its interactions with cyclins and the APC/C.
- **DNA Replication:** By stabilizing CDT1 and regulating factors vital for DNA replication licensing.
- **Deubiquitination:** Specific mechanisms involving the removal of ubiquitin from target proteins, affecting their degradation and functional stability.
- **Response to DNA Damage:** May play a role in signaling pathways that respond to DNA damage by influencing the stability and functionality of repair proteins.

Overall, USP37 serves as an important regulatory protein in maintaining cell cycle integrity and ensuring proper cell division, with potential implications in aging and various diseases, particularly cancer.