### PPP2R2A Gene Overview

**Gene Symbol:** PPP2R2A  
**Location:** Chromosome 8 (8p12)  
**Protein Product:** Regulatory subunit B55α of Protein Phosphatase 2A (PP2A)

**Function:** The PPP2R2A gene encodes a regulatory subunit of the serine/threonine protein phosphatase 2A (PP2A), which plays a critical role in cell growth and division by negatively regulating various signaling pathways. The B55 subfamily, including the α isoform encoded by PPP2R2A, is instrumental in directing the substrate specificity and enhancing the catalytic activity of the phosphatase. Its involvement in the dephosphorylation of proteins like WEE1 is crucial for cell cycle regulation, particularly at the G2/M checkpoint.

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### 1. Related Genes

The functionality and regulatory roles of PPP2R2A relate to several other genes:

- **PPP2CA**: Catalytic subunit of PP2A, which forms the core enzyme along with regulatory subunits like PPP2R2A.
- **WEE1**: A kinase that is involved in the phosphorylation of targets for cell cycle progression; its protein levels are modulated by PPP2R2A.
- **CDK1**: Cyclin-dependent kinase involved in regulating the G2/M transition; consecutive phosphorylation/dephosphorylation events mediated by PP2A affect CDK1 activity.
- **PTEN**: A tumor suppressor that can interact with the PP2A complex.
- **MYC**: An oncogene where PP2A has been shown to be a negative regulator.

Additionally, the regulatory network that includes genes such as **CDKN1A (p21)** and **CCNB1 (Cyclin B1)** might also interact with PPP2R2A functionally.

### 2. Aging and Age-Related Diseases

Research suggests that the dysregulation of PP2A activity (including alterations in PPP2R2A expression) is implicated in various age-related diseases, including:

- **Cancer**: Reduced PP2A activity is frequently observed in tumors, and PPP2R2A has tumor-suppressive roles. Mutations or epigenetic silencing of PPP2R2A have been linked to different malignancies.
- **Neurodegenerative diseases**: The regulation of signaling pathways associated with cellular stress and apoptosis, which involves PPP2R2A, may contribute to diseases such as Alzheimer's disease by affecting tau phosphorylation.
- **Metabolic disorders**: PP2A activity influences various metabolic pathways, and alterations can be associated with insulin signaling and other metabolic perturbations in aging populations.

### 3. Drug Interactions

Specific drugs that have been reported to interact with PP2A through modulation of its regulatory subunits (including PPP2R2A) include:

- **Cancer therapeutics**: Drugs like **Okadaic acid**, a potent inhibitor of Ser/Thr phosphatases, can lead to dysregulated PP2A signaling.
- **Ivermectin**: Has demonstrated potential to activate PP2A and thus has implications in studies relating to tumor suppression.
- **Antipsychotic medications**: Some studies have explored the interaction of atypical antipsychotics with PP2A signaling pathways.

While these drug interactions are noteworthy, the clinical significance may vary, and the drug classes involved still require thorough research to elucidate precise mechanisms.

### 4. Pathways and Biological Processes

PPP2R2A is involved in several critical biological pathways, including:

- **Cell Cycle Regulation**: Particularly modulation of the G2/M checkpoint through WEE1 dephosphorylation.
- **Apoptosis**: Through the regulation of key signaling pathways that execute cell death through phosphorylation status alterations.
- **Signal Transduction**: Influences various cascades like MAPK/ERK and PI3K/AKT pathways, affecting cellular responses to growth signals.
- **Metabolic Processes and Responses to Nutrient Signals**: Its regulation roles can affect various metabolic pathways.

### Summary

In summary, the PPP2R2A gene encodes a significant regulatory subunit of PP2A, with implications in cell cycle regulation, aging, and disease. Continued research is likely to reveal more intricate interactions and potential therapeutic avenues surrounding this gene.