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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Caspase activation, inhibition, and reactivation: a mechanistic view

Yigong Shi1

  • 1Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA. yshi@molbio.princeton.edu

Protein Science : a Publication of the Protein Society
|July 27, 2004
PubMed

Insights

Programmed cell death (apoptosis) is executed by caspases, which are activated from inactive forms. Inhibitor-of-apoptosis proteins (IAPs) regulate caspases, but this inhibition can be reversed by specific binding motifs.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Caspases are cysteine proteases crucial for executing programmed cell death (apoptosis).
  • Caspases are synthesized as inactive zymogens and activated through a proteolytic cascade during apoptosis.
  • The activity of caspases is regulated by the inhibitor-of-apoptosis (IAP) protein family.

Purpose of the Study:

  • To review recent advances in understanding caspase activation and regulation.
  • To highlight the molecular mechanisms of IAP-mediated inhibition and its reversal.
  • To discuss structural and biochemical insights from mammalian and Drosophila studies.

Main Methods:

  • Review of recent structural and biochemical studies.
  • Analysis of caspase activation cascades.
  • Investigation of IAP-binding tetrapeptide motifs and their function.

Main Results:

  • Caspase activation follows a defined cascade from inactive zymogens.
  • Inhibitor-of-apoptosis proteins (IAPs) bind and inhibit active caspases.
  • Proteins with an IAP-binding motif can release caspases from IAP inhibition.

Conclusions:

  • Recent studies elucidate the molecular basis of caspase regulation by IAPs.
  • Understanding these mechanisms is key to controlling apoptosis.
  • Comparative studies in mammals and Drosophila provide conserved insights into cell death pathways.

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