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Published on: August 4, 2019

Inhibition of TFII-I-dependent cell cycle regulation by p53

Zana P Desgranges1, Jinwoo Ahn, Maria B Lazebnik

  • 1Program in Immunology, Sackler School of Graduate Biomedical Sciences, Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.

Molecular and Cellular Biology
|November 30, 2005
PubMed

Insights

Transcription factor TFII-I promotes cell cycle progression by activating cyclin D1. Genotoxic stress triggers TFII-I degradation, leading to cell cycle arrest, highlighting its role in proliferation control.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The transcription factor TFII-I is known to be tyrosine phosphorylated by extracellular growth signals, activating growth-promoting genes.
  • Its direct impact on the cell cycle profile remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of TFII-I in cell cycle regulation and proliferation.
  • To elucidate the mechanisms by which TFII-I controls cyclin D1 expression and cell cycle progression.

Main Methods:

  • Analysis of TFII-I recruitment to the cyclin D1 promoter.
  • Investigation of TFII-I ubiquitination and degradation pathways.
  • Assessment of cell cycle profiles following TFII-I manipulation.
  • Site-directed mutagenesis to study tyrosine phosphorylation sites.

Main Results:

  • TFII-I is recruited to the cyclin D1 promoter and activates its transcription under normal growth conditions.
  • Genotoxic stress induces p53- and ATM-dependent ubiquitination and proteasomal degradation of TFII-I.
  • TFII-I expression accelerates entry and exit from S phase and overcomes p53-mediated cell cycle arrest.
  • Tyrosine phosphorylation at positions 248 and 611 is crucial for TFII-I's growth signal-mediated transcriptional activity and cell cycle control.

Conclusions:

  • TFII-I acts as a critical growth signal-dependent transcriptional activator for cell cycle control and proliferation.
  • Genotoxic stress-induced degradation of TFII-I is a key mechanism for initiating cell cycle arrest.

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