La mitogaligine, protéine de la mort cellulaire programmée : localisation nucléaire, conséquences de modifications post-traductionnelles potentielles et interaction fonctionnelle avec Mcl-1

Abstract : Mitogaligin is a protein encoded by galig, a cell death gene. Previously, it has been shown in our laboratory, that this mitochondrial protein induces cell death through an alternative pathway of apoptosis. In this report, we show that mitogaligin can also be addressed to the nucleus where it exhibits also a cytotoxic activity. The nuclear localization signal is not conventional, based on a repetition of amino acids, and function only if the mitochondrial localization signal is inactivated. Thus, the cytotoxicity of mitogaligin could be regulated by its subcellular localization. A large number of apoptotic proteins are regulated by post-translational modifications. Mitogaligin has several potential sites of phosphorylation. Some of them have been mutated to highlight the possible role of phosphorylation in the mitogaligin activity. The wild type protein undergoes one or several proteolytic cuts. Replacement of the threonines 29 and 73 by phospho-mimetic residue decrease mitogaligin proteolysis and also mitogaligin cytotoxicity. The same type of mutation on threonine 38 and serine 39 induces a re-localization of mitogaligin outside mitochondria. The last part of the manuscript focuses on the functional interaction between mitogaligin and Mcl-1, an anti-apoptotic protein of the Bcl-2 family. Coexpression of galig and Mcl-1 significantly reduces galig cell death and overexpression of galig reduces production of endogenous Mcl-1. Therefore, galig could represent a therapeutic target in order to restore cell death in cells overexpressing anti-apoptotic proteins of the Bcl-2 family.
Document type :
Theses
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-00635381
Contributor : Abes Star <>
Submitted on : Tuesday, October 25, 2011 - 11:03:22 AM
Last modification on : Wednesday, June 27, 2018 - 8:24:02 AM
Long-term archiving on : Thursday, January 26, 2012 - 2:43:10 PM

File

pauline.robinet_1927.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00635381, version 1

Collections

Citation

Pauline Robinet. La mitogaligine, protéine de la mort cellulaire programmée : localisation nucléaire, conséquences de modifications post-traductionnelles potentielles et interaction fonctionnelle avec Mcl-1. Sciences agricoles. Université d'Orléans, 2010. Français. ⟨NNT : 2010ORLE2082⟩. ⟨tel-00635381⟩

Share

Metrics

Record views

502

Files downloads

761