Human TTC5, a novel tetratricopeptide repeat domain containing gene, activates p53 and inhibits AP-1 pathway

Ying Xiong1, Lan Wang, Weiwei Deng

  • 1Chinese National Human Genome Center, Beijing, 100176, China.

Insights

The novel gene TTC5 (tetratricopeptide repeat domain 5) activates the p53 pathway and inhibits the AP-1 pathway, impacting cell viability. This discovery offers new insights into cell signaling regulation and potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The transcription factors p53 and AP-1 are crucial regulators of cellular processes like proliferation, transformation, and apoptosis.
  • TTC5 (tetratricopeptide repeat domain 5) is a novel human gene belonging to the TTC protein family, previously implicated in cellular stress response.

Purpose of the Study:

  • To investigate the role of the novel human gene TTC5 in regulating cell signaling pathways and cell viability.
  • To elucidate the molecular mechanisms by which TTC5 influences the p53 and AP-1 signaling pathways.

Main Methods:

  • Overexpression of TTC5 in human cells.
  • Analysis of p53 and AP-1 pathway components, including gene expression, protein levels, and phosphorylation.
  • Cell proliferation assays and cell cycle analysis (S phase arrest).

Main Results:

  • TTC5 significantly activated the p53 pathway, up-regulating p53 and p21 expression.
  • TTC5 significantly inhibited AP-1 transcriptional activity, c-Jun expression, and phosphorylation.
  • TTC5 down-regulated the expression and phosphorylation of JNK/SAPK, upstream regulators of AP-1.
  • Overexpression of TTC5 repressed cell proliferation and induced S phase cell cycle arrest.

Conclusions:

  • TTC5 plays a significant role in regulating cell viability through modulation of the p53 and AP-1 signaling pathways.
  • TTC5 acts as a key regulator, activating p53 while inhibiting AP-1 activity, thereby influencing cell cycle progression and proliferation.
  • These findings highlight TTC5 as a potential target for therapeutic interventions in diseases involving aberrant cell signaling.

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