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Nuclear FAK: a new mode of gene regulation from cellular adhesions

Ssang-Taek Steve Lim1

  • 1Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, USA. stlim@southalabama.edu

Molecules and Cells
|May 21, 2013
PubMed

Insights

Focal adhesion kinase (FAK) acts in the nucleus to control cell proliferation and inflammation by degrading key proteins. Nuclear FAK offers new therapeutic targets for inflammatory diseases.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Focal adhesion kinase (FAK) is a protein tyrosine kinase (PTK) primarily known for cytoplasmic roles in cell migration and proliferation.
  • Recent research highlights FAK's novel functions within the cell nucleus.
  • FAK signaling extends beyond cell adhesion to directly influence nuclear processes.

Purpose of the Study:

  • To review the emerging roles of nuclear FAK in regulating transcription factors.
  • To discuss the implications of nuclear FAK in cellular processes like proliferation and inflammation.
  • To explore the therapeutic potential of targeting nuclear FAK in disease.

Main Methods:

  • This review synthesizes findings from recent experimental studies on FAK localization and function.
  • Analysis of FAK's interactions with transcription factors and its role in ubiquitination pathways.
  • Examination of FAK's nuclear translocation under various cellular conditions, including pharmacological inhibition.

Main Results:

  • Nuclear FAK promotes the degradation of p53 and GATA4 via ubiquitination, enhancing cell proliferation.
  • Nuclear FAK acts as a co-transcriptional regulator, modulating gene transcription.
  • FAK nuclear translocation is notably increased under conditions of de-adhesion and pharmacological FAK inhibition.

Conclusions:

  • FAK signaling represents a paradigm shift, extending from cell adhesions to the nucleus.
  • Nuclear FAK plays critical roles in regulating gene expression, cell proliferation, and inflammatory responses.
  • Targeting nuclear FAK with inhibitors presents a promising therapeutic strategy for inflammatory diseases.

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