Incomplete T-cell receptor-β peptides target the mitochondrion and induce apoptosis

Nir Shani, Hila Rubin-Lifshitz, Yifat Peretz-Cohen, Ketty Shkolnik, Vera Shinder, Michal Cohen-Sfady, Yaron Shav-Tal, Mira Barda-Saad, Dov Zipori*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The default pathway of cell-surface T-cell receptor (TCR) complex formation, and the subsequent transport to the membrane, is thought to entail endoplasmic reticulum (ER) localization followed by proteasome degradation of the unassembled chains. We show herein an alternative pathway: short, incomplete pep - tide versions of TCRβ naturally occur in the thymus. Such peptides, which have minimally lost the leader sequence or have been massively truncated, leaving only the very C terminus intact, are sorted preferentially to the mitochondrion. As a consequence of the mitochondrial localization, apoptotic cell death is induced. Structure function analysis showed that both the specific localization and induction of apoptosis depend on the trans - membrane domain (TMD) and associated residues at the COOH-terminus of TCR. Truncated forms of TCR, such as the short peptides that we detected in the thymus, may be products of protein degradation within thymocytes. Alternatively, they may occur through the translation of truncated mRNAs resulting from unfruitful rearrangement or from germline transcription. It is proposed that mitochondria serve as a subcellular sequestration site for incomplete TCR molecules.

Original languageEnglish
Pages (from-to)3530-3541
Number of pages12
JournalBlood
Volume113
Issue number15
DOIs
StatePublished - 9 Apr 2009
Externally publishedYes

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