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'Tissue' transglutaminase in cell death: a downstream or a multifunctional upstream effector?

G Melino1, M Piacentini

  • 1Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Dept. Experimental Medicine, University of Rome Tor Vergata, Italy. gerry-melino@uniromaZ.it

FEBS Letters
|July 25, 1998
PubMed

Insights

Tissue transglutaminase (tTG) is a multifunctional enzyme crucial for regulating apoptosis. Recent findings reveal its complex role in cell death pathways, extending beyond its traditional function in protein crosslinking.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Apoptosis involves morphological changes regulated by proteins like tissue transglutaminase (tTG).
  • tTG was initially recognized for its role in crosslinking proteins to prevent cellular leakage and reduce inflammation.
  • Emerging evidence suggests tTG has a more intricate function in the upstream regulation of apoptosis.

Purpose of the Study:

  • To explore the multifaceted role of tissue transglutaminase (tTG) in the regulation of apoptosis.
  • To elucidate the complex molecular mechanisms underlying tTG's involvement in cell death pathways.

Main Methods:

  • Analysis of tTG's function as a GTP-binding protein in signal transduction.
  • Investigation of tTG's substrate specificity in cytosolic and nuclear compartments.
  • Examination of tTG's regulation by calcium ions, GTP, S-nitrosylation, and polyamines.

Main Results:

  • tTG functions as a GTP-binding protein, participating in signal transduction.
  • tTG exhibits specific binding and crosslinking of particular cytosolic and nuclear substrates.
  • tTG's activity is modulated by Ca2+, GTP, S-nitrosylation, and polyamines, indicating precise control.

Conclusions:

  • The role of tissue transglutaminase (tTG) in regulating the balance between cell survival and death is complex.
  • tTG is a key regulator in the apoptotic machinery, with functions beyond simple crosslinking.
  • tTG's specific interactions and regulatory mechanisms highlight its critical involvement in apoptosis.

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