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Signaling Lessons from Death Receptors
Author(s) -
Dixit Vishva M.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.311.2
Subject(s) - fadd , ubiquitin , death domain , microbiology and biotechnology , receptor , signal transduction , sumo protein , ubiquitin ligase , phosphorylation , dephosphorylation , deubiquitinating enzyme , chemistry , biology , phosphatase , caspase , programmed cell death , biochemistry , apoptosis , gene
It was thought that receptors signaled either by serving as ion channels or by altering phosphorylation‐dephosphorylation events. Work in my laboratory in the mid‐nineties conclusively showed that death domain‐containing receptors signaled by an entirely new mechanism, specifically, adapter (FADD)‐mediated recruitment and direct activation of a death protease (FLICE/caspase‐8). Subsequent studies by my own and other laboratories showed that this was a universal mechanism deployed by death receptors. Further study of the NF‐kB inducing death receptor, TNFR1, has recently unveiled another new signaling mechanism, that we have termed “ubiquitin editing.” Ubiquitin editing is mediated by a highly conserved single polypeptide protein, termed A20, which contains both a ubiquitin hydrolase and a ubiquitin ligase domain. Initially, this seemed counterintuitive as it was akin to a molecule possessing both kinase and phosphatase activities –– the ultimate futile cycle! We found, however, that these seemingly contradictory activities actually act in concert to attenuate cytokine signaling.