Implication of different domains of the Leishmania major metacaspase in cell death and autophagy

M. Casanova*, I. J. Gonzalez, C. Sprissler, H. Zalila, M. Dacher, L. Basmaciyan, G. F. Späth, N. Azas, N. Fasel

*この研究の対応する著者

研究成果: Article査読

27 被引用数 (Scopus)

抄録

Metacaspases (MCAs) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. The role of MCAs is subject to debate: roles incell cycle control, in cell death or even in cell survival have been suggested. In this study, using a Leishmania major MCA-deficient strain, we showed that L. major MCA (LmjMCA) not only had a role similar to caspases in cell death but also in autophagy and this through different domains. Upon cell death induction by miltefosine or H2O2, LmjMCA is processed, releasing the catalytic domain, which activated substrates via its catalytic dyad His/Cys and a proline-rich C-terminal domain. The C-terminal domain interacted with proteins, notably proteins involved in stress regulation, such as the MAP kinase LmaMPK7 or programmed cell death like the calpain-like cysteine peptidase. We also showed a new role of LmjMCA in autophagy, acting on or upstream of ATG8, involving Lmjmca gene overexpression and interaction of the C-terminal domain of LmjMCA with itself and other proteins. These results allowed us to propose two models, showing the role of LmjMCA in the cell death and also in the autophagy pathway, implicating different protein domains.

本文言語English
論文番号e1933
ジャーナルCell Death and Disease
6
10
DOI
出版ステータスPublished - 2015 10月 1
外部発表はい

ASJC Scopus subject areas

  • 免疫学
  • 細胞および分子神経科学
  • 細胞生物学
  • 癌研究

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