Skip to Main content Skip to Navigation
Journal articles

Peptides Targeting the PDZ Domain of PTPN4 Are Efficient Inducers of Glioblastoma Cell Death

Abstract : PTPN4, a human tyrosine phosphatase, protects cells against apoptosis. This protection could be abrogated by targeting the PDZ domain of this phosphatase with a peptide mimicking the C-terminal sequence of the G protein of an attenuated rabies virus strain. Here, we demonstrate that glioblastoma death is triggered upon intracellular delivery of peptides, either from viral origin or from known endogenous ligands of PTPN4-PDZ, such as the C terminus sequence of the glutamate receptor subunit GluN2A. The killing efficiency of peptides closely reflects their affinities for the PTPN4-PDZ. The crystal structures of two PTPN4-PDZ/peptide complexes allow us to pinpoint the main structural determinants of binding and to synthesize a peptide of high affinity for PTPN4-PDZ enhancing markedly its cell death capacity. These results allow us to propose a potential mechanism for the efficiency of peptides and provide a target and a robust framework for the design of new pro-death compounds.
Complete list of metadatas

https://hal-pasteur.archives-ouvertes.fr/pasteur-02883997
Contributor : Nicolas Wolff <>
Submitted on : Monday, June 29, 2020 - 3:49:24 PM
Last modification on : Tuesday, July 7, 2020 - 3:35:14 AM

Links full text

Identifiers

Collections

Citation

Nicolas Babault, Florence Cordier, Mireille Lafage, Joseph Cockburn, Ahmed Haouz, et al.. Peptides Targeting the PDZ Domain of PTPN4 Are Efficient Inducers of Glioblastoma Cell Death. Structure, Elsevier (Cell Press), 2011, 19 (10), pp.1518-1524. ⟨10.1016/j.str.2011.07.007⟩. ⟨pasteur-02883997⟩

Share

Metrics

Record views

28