regulation of telomerase activity

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of telomerase activity, the catalysis of the reaction: deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). Telomerases catalyze extension of the 3'- end of a DNA strand by one deoxynucleotide at a time using an internal RNA template that encodes the telomeric repeat sequence. [EC:2.-.-.-, GOC:ai]

Telomerase activity is tightly regulated to prevent uncontrolled cell proliferation and maintain genomic stability. The enzyme telomerase adds repetitive DNA sequences (TTAGGG) to the ends of chromosomes, known as telomeres, compensating for the loss that occurs during DNA replication. This process is essential for maintaining chromosome integrity and preventing cellular senescence.

**Regulation of Telomerase Activity:**

**1. Transcriptional Regulation:**
- **TERT (Telomerase Reverse Transcriptase) gene:** This gene encodes the catalytic subunit of telomerase. Its expression is tightly controlled and is generally low in most somatic cells.
- **Transcription factors:** Various transcription factors, including c-Myc, E2F1, and NF-κB, can bind to regulatory elements in the TERT gene, promoting its transcription in response to specific cellular signals.
- **Epigenetic modifications:** DNA methylation and histone modifications can influence TERT gene expression. For example, hypermethylation of the TERT promoter can suppress its transcription.

**2. Post-Translational Regulation:**
- **Protein stability:** Telomerase subunits are subject to ubiquitination and proteasomal degradation. This process ensures that telomerase activity is tightly regulated and prevents its accumulation.
- **Protein phosphorylation:** Phosphorylation events can affect the activity and stability of telomerase subunits.

**3. Subcellular Localization:**
- **Nuclear transport:** Telomerase must be transported from the cytoplasm to the nucleus to access telomeres. This process is regulated by specific nuclear localization signals (NLS) within telomerase subunits.
- **Association with telomeres:** Telomerase associates with telomeres through interactions with specific proteins, including TRF1 and TRF2, which are components of the shelterin complex.

**4. Cellular Signals:**
- **Growth factors:** Growth factors, such as epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), can stimulate telomerase activity.
- **Oxidative stress:** Reactive oxygen species (ROS) can induce telomerase expression, potentially as a protective mechanism against DNA damage.
- **Cellular senescence:** During replicative senescence, telomerase activity is typically downregulated, contributing to the cessation of cell division.

**5. Disease Implications:**
- **Cancer:** Dysregulation of telomerase activity is commonly observed in cancer cells, allowing them to evade senescence and proliferate indefinitely.
- **Aging:** Telomere shortening and reduced telomerase activity contribute to the aging process.

**Overall, the regulation of telomerase activity is a complex and multifaceted process involving transcriptional, post-translational, and cellular signaling mechanisms. This intricate regulation ensures proper telomere maintenance and cellular homeostasis, while also contributing to the pathogenesis of various diseases.**'
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Proteins (2)

Compounds (28)