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Accumulation of a form of p27(Kip1) not associated with Cdk-cyclin complexes in transforming growth

M Taipale1, E Tiihonen, A Heiskanen

  • 1Department of Virology, University of Helsinki, Helsinki, FIN-00014, Finland.

Experimental Cell Research
|August 16, 2000
PubMed

Insights

Transforming growth factor-beta induces a specific form of p27(Kip1) in growth-arrested cells. This non-bound p27(Kip1) may act as a reservoir to inhibit Cdk2-cyclin E activity, promoting cell cycle arrest.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • p27(Kip1) is a cyclin-dependent kinase inhibitor.
  • Transforming growth factor-beta (TGF-β) can inhibit cell proliferation.
  • TGF-β induces p27(Kip1) translocation to Cdk2-cyclin E complexes, inhibiting activity without changing protein levels.

Purpose of the Study:

  • Investigate the mechanism of TGF-β-induced cell cycle arrest related to p27(Kip1).
  • Characterize the specific form of p27(Kip1) that accumulates during growth arrest.
  • Determine the interaction status of inducible p27(Kip1) with cyclin-dependent kinase complexes.

Main Methods:

  • Utilized Mv1Lu epithelial cells.
  • Applied transforming growth factor-beta, serum starvation, and contact inhibition as growth arrest stimuli.
  • Employed a specific monoclonal antibody for detecting native p27(Kip1).
  • Assessed p27(Kip1) interactions with cyclin-dependent kinase/cyclin complexes.

Main Results:

  • TGF-β induces the accumulation of a specific subpopulation of p27(Kip1) in growth-arrested cells.
  • This inducible p27(Kip1) is detectable only by an antibody recognizing its native form.
  • The accumulation of this p27(Kip1) subset correlates with G1 arrest induced by TGF-β, serum starvation, or contact inhibition.
  • Unlike the majority of p27(Kip1), the inducible form is not bound to cyclin-dependent kinase/cyclin complexes.

Conclusions:

  • Growth-arresting treatments lead to the accumulation of non-cyclin-dependent kinase-bound p27(Kip1).
  • This accumulation suggests a reservoir function for p27(Kip1) in inhibiting Cdk2-cyclin E activity.
  • The findings provide new insights into the regulation of cell cycle progression by p27(Kip1).

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