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Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development

P Zhang1, C Wong, R A DePinho

  • 1Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 10461 USA.

Genes & Development
|October 24, 1998
PubMed

Insights

Cell cycle exit and differentiation depend on cyclin-dependent kinase (CDK) inhibitors p27(KIP1) and p57(KIP2). These proteins redundantly control cell differentiation in lens fiber cells and placental trophoblasts.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Cell cycle exit is crucial for terminal differentiation in various cell types.
  • The retinoblastoma protein (Rb) is involved in cell cycle exit and differentiation, and is regulated by cyclin-dependent kinases (Cdks).
  • The specific effectors that reduce Cdk activity to activate Rb in tissues like the lens remain largely unknown.

Purpose of the Study:

  • To identify the key effectors that down-regulate Cdk activity, leading to Rb activation.
  • To investigate the role of Cdk inhibitors in controlling cell cycle exit and differentiation in specific cell types.

Main Methods:

  • Utilized multiple mutant mouse models to study gene function.
  • Analyzed the redundant functions of p27(KIP1) and p57(KIP2) in vivo.
  • Examined cell cycle exit and differentiation in lens fiber cells and placental trophoblasts.

Main Results:

  • Demonstrated that p27(KIP1) and p57(KIP2) function redundantly.
  • Showed these Cdk inhibitors are essential for cell cycle exit and differentiation of lens fiber cells.
  • Confirmed their redundant role in the differentiation of placental trophoblasts.

Conclusions:

  • p27(KIP1) and p57(KIP2) are critical terminal effectors in cell differentiation pathways.
  • These Cdk inhibitors play a redundant, essential role in controlling cell cycle exit and terminal differentiation.
  • The findings elucidate a key mechanism regulating differentiation in multiple tissues.

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