Tissue transglutaminase is a multifunctional BH3-only protein

Carlo Rodolfo, Elisabetta Mormone, Paola Matarrese, Fabiola Ciccosanti, Maria Grazia Farrace, Elvira Garofano, Lucia Piredda, Gian Maria Fimia, Walter Malorni, Mauro Piacentini

Research output: Contribution to journalArticle

Abstract

Tissue transglutaminase (TG2) protein accumulates to high levels in cells during early stages of apoptosis both in vivo and in vitro. The analysis of the TG2 primary sequence showed the presence of an eight amino acid domain, sharing 70% identity with the Bcl-2 family BH3 domain. Cell-permeable peptides, mimicking the domain sequence, were able to induce Bax conformational change and translocation to mitochondria, mitochondrial depolarization, release of cytoclirome c, and cell death. Moreover, we found that the TG2-BH3 peptides as well as TG2 itself were able to interact with the pro-apoptotic Bcl-2 family member Bax, but not with anti-apoptotic members Bcl-2 and Bcl-XL. Mutants in the TG2-BH3 domain failed to sensitize cells toward apoptosis. In TG2-overexpressing cells about half of the protein is localized on the outer mitochondrial membrane where, upon cell death induction, it cross-links many protein substrates including Bax. TG2 is the first member of a new subgroup of multifunctional BH3-only proteins showing a large mass size (80 kDa) and enzymatic activity.

Original languageEnglish
Pages (from-to)54783-54792
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number52
DOIs
Publication statusPublished - Dec 24 2004

ASJC Scopus subject areas

  • Biochemistry

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    Rodolfo, C., Mormone, E., Matarrese, P., Ciccosanti, F., Farrace, M. G., Garofano, E., Piredda, L., Fimia, G. M., Malorni, W., & Piacentini, M. (2004). Tissue transglutaminase is a multifunctional BH3-only protein. Journal of Biological Chemistry, 279(52), 54783-54792. https://doi.org/10.1074/jbc.M410938200