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'Tissue' transglutaminase in cell death: a downstream or a multifunctional upstream effector?
1Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Dept. Experimental Medicine, University of Rome Tor Vergata, Italy. gerry-melino@uniromaZ.it
FEBS Letters
|July 25, 1998
Summary
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.