Type 2 transglutaminase is involved in the autophagy-dependent clearance of ubiquitinated proteins

M. D'Eletto, M. G. Farrace, F. Rossin, F. Strappazzon, G. Di Giacomo, F. Cecconi, G. Melino, S. Sepe, S. Moreno, G. M. Fimia, L. Falasca, R. Nardacci, M. Piacentini

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Eukaryotic cells are equipped with an efficient quality control system to selectively eliminate misfolded and damaged proteins, and organelles. Abnormal polypeptides that escape from proteasome-dependent degradation and aggregate in the cytosol can be transported via microtubules to inclusion bodies called aggresomes, where misfolded proteins are confined and degraded by autophagy. Here, we show that Type 2 transglutaminase (TG2) knockout mice display impaired autophagy and accumulate ubiquitinated protein aggregates upon starvation. Furthermore, p62-dependent peroxisome degradation is also impaired in the absence of TG2. We also demonstrate that, under cellular stressful conditions, TG2 physically interacts with p62 and they are localized in cytosolic protein aggregates, which are then recruited into autophagosomes, where TG2 is degraded. Interestingly, the enzyme's crosslinking activity is activated during autophagy and its inhibition leads to the accumulation of ubiquitinated proteins. Taken together, these data indicate that the TG2 transamidating activity has an important role in the assembly of protein aggregates, as well as in the clearance of damaged organelles by macroautophagy.

Original languageEnglish
Pages (from-to)1228-1238
Number of pages11
JournalCell Death and Differentiation
Volume19
Issue number7
DOIs
Publication statusPublished - Jul 2012

Fingerprint

Ubiquitinated Proteins
Autophagy
Organelles
Peroxisomes
Inclusion Bodies
Eukaryotic Cells
Proteasome Endopeptidase Complex
Starvation
Knockout Mice
Microtubules
Quality Control
Cytosol
Proteins
Peptides
transglutaminase 2
Enzymes
Protein Aggregates

Keywords

  • autophagy
  • MG132
  • p62
  • transglutaminase 2
  • ubiquitinated proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Type 2 transglutaminase is involved in the autophagy-dependent clearance of ubiquitinated proteins. / D'Eletto, M.; Farrace, M. G.; Rossin, F.; Strappazzon, F.; Giacomo, G. Di; Cecconi, F.; Melino, G.; Sepe, S.; Moreno, S.; Fimia, G. M.; Falasca, L.; Nardacci, R.; Piacentini, M.

In: Cell Death and Differentiation, Vol. 19, No. 7, 07.2012, p. 1228-1238.

Research output: Contribution to journalArticle

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