Vanadate activated Akt and promoted S phase entry

Zhuo Zhang1, Ning Gao, Hengjun He

  • 1Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.

Insights

Vanadate treatment promotes cell cycle progression by activating Akt (protein kinase B). This pathway involves the retinoblastoma protein (pRb) and transcription factor E2F1, driving cells into S phase.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein kinase B (Akt) and phosphatidylinositol 3-kinase (PI3K) regulate cell growth, survival, and metabolism.
  • Akt influences transcription and translation, impacting cell proliferation.
  • Transcription factor E2F is a key regulator of cell cycle progression, particularly the G1 to S phase transition.

Purpose of the Study:

  • To investigate the role of Akt in vanadate-induced cell cycle progression.
  • To elucidate the involvement of the E2F-pRb pathway in vanadate-mediated S phase entry.

Main Methods:

  • Vanadate treatment of C141 cells.
  • Analysis of cell cycle distribution (S phase percentage).
  • Measurement of cyclin E, cyclin A, pRb phosphorylation, and E2F1 release.
  • Assessment of Akt kinase activity and phosphorylation.
  • Inhibition of Akt using chemical inhibitors and dominant-negative mutants.

Main Results:

  • Vanadate increased S phase percentage, cyclin E, and cyclin A expression.
  • Vanadate induced pRb phosphorylation and E2F1 release.
  • Vanadate enhanced Akt kinase activity and phosphorylation.
  • Akt inhibition abrogated vanadate-induced S phase entry and reduced cyclin E, E2F1, and pRb phosphorylation.

Conclusions:

  • Akt plays a critical role in vanadate-induced cell proliferation.
  • The Akt-mediated pathway facilitates G1 to S phase transition via the E2F-pRb axis.

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