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"Tissue" transglutaminase and apoptosis

F Autuori1, M G Farrace, S Oliverio

  • 1Department of Biology, University of Rome Tor Vergata, Italy.

Advances in Biochemical Engineering/Biotechnology
|October 2, 1998
PubMed
Summary

Tissue transglutaminase (tTG) plays a key role in programmed cell death (apoptosis). This enzyme cross-links proteins, forming a scaffold that protects cells during apoptosis, and its expression increases during this process.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Tissue transglutaminase (tTG) is an enzyme involved in protein cross-linking.
  • Apoptosis, or programmed cell death, is a critical cellular process.
  • The precise role of tTG in apoptosis has been an area of investigation.

Purpose of the Study:

  • To elucidate the function of tissue transglutaminase (tTG) in the process of apoptosis.
  • To investigate how tTG influences cellular susceptibility to programmed cell death.

Main Methods:

  • Studied the Ca(2+)-dependent cross-linking activity of tTG on intracellular proteins.
  • Analyzed tTG mRNA transcription in response to apoptosis induction.
  • Utilized cell lines with tTG overexpression and antisense tTG cDNA transfection.

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  • Identified tTG substrate proteins in apoptotic cells.
  • Main Results:

    • tTG catalyzes the formation of an SDS-insoluble protein scaffold during apoptosis.
    • tTG expression and mRNA are induced as a consequence of apoptosis induction.
    • Overexpression of tTG increases cellular susceptibility to apoptosis.
    • Antisense tTG cDNA transfection significantly reduces both spontaneous and induced apoptosis.
    • Many tTG substrates in apoptotic cells are also substrates of caspases.

    Conclusions:

    • Tissue transglutaminase (tTG) plays a pivotal role in promoting apoptosis.
    • The formation of a tTG-dependent protein scaffold contributes to cellular changes during programmed cell death.
    • tTG's substrates overlap with caspase substrates, suggesting intricate crosstalk in apoptotic pathways.