The molecular interaction of Fas and FAP-1: A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis

Junn Yanagisawa, Motoo Takahashi, Hiroaki Kanki, Hiroko Yano-Yanagisawa, Tetsushi Tazunoki, Eiji Sawa, Tsuyoshi Nishitoba, Masaru Kamishohara, Eiichi Kobayashi, Shiro Kataoka, Takaaki Sato

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Fas (APO-1/CD95), which is a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. A protein tyrosine phosphatase, Fas-associated phosphatase-1 (FAP-1), that was previously identified as a Fas binding protein interacts with the C-terminal 15 amino acids of the regulatory domain of the Fas receptor. To identify the minimal region of the Fas C-terminal necessary for binding to FAP-1, we employed an in vitro inhibition assay of Fas/FAP-1 binding using a series of synthetic peptides as well as a screen of random peptide libraries by the yeast two-hybrid system. The results showed that the C-terminal three amino acids (SLV) of human Fas were necessary and sufficient for its interaction with the third PDZ (GLGF) domain of FAP-1. Furthermore, the direct cytoplasmic microinjection of this tripeptide (Ac-SLV) resulted in the induction of Fas-mediated apoptosis in a colon cancer cell line that expresses both Fas and FAP-1. Since t(S/T)X(V/L/I) motifs in the C termini of several other receptors have been shown to interact with PDZ domain in signal transducing molecules, this may represent a general motif for protein- protein interactions with important biological functions.

Original languageEnglish
Pages (from-to)8539-8545
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number13
DOIs
StatePublished - Mar 28 1997

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