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Apoptosis and autophagy: Regulation of caspase-9 by phosphorylation

Lindsey A Allan1, Paul R Clarke

  • 1Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK.

The FEBS Journal
|October 1, 2009
PubMed

Insights

Apoptosis, a crucial cell death process, is regulated by caspase-9 activation. New research reveals caspase-9 phosphorylation by protein kinases offers a key regulatory mechanism in development and disease.

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Apoptosis is vital for development, homeostasis, and disease, with the intrinsic pathway crucial for many stimuli.
  • Caspase-9 is central to the mitochondrial apoptotic pathway, activated within the apoptosome complex.
  • This pathway is tightly regulated, particularly at apoptosome formation and caspase-9 activation stages.

Purpose of the Study:

  • To review recent advances in understanding caspase-9 regulation.
  • To discuss the role of caspase-9 phosphorylation in apoptosis.
  • To explore implications in development and pathological states like cancer.

Main Methods:

  • Literature review of recent research on caspase-9 phosphorylation.
  • Analysis of protein kinase interactions with caspase-9.
  • Discussion of experimental findings and their biological significance.

Main Results:

  • Caspase-9 is a direct target for regulatory phosphorylation by various protein kinases.
  • These kinases are activated by diverse stimuli including growth factors, osmotic stress, and mitosis.
  • Phosphorylation represents a significant regulatory mechanism for caspase-9 activity.

Conclusions:

  • Caspase-9 phosphorylation by protein kinases is a key regulatory step in apoptosis.
  • Understanding these phosphorylation events is crucial for deciphering apoptosis regulation.
  • This knowledge has implications for development, tissue homeostasis, and diseases such as cancer.

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