title: 14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules.
abstract: A20, a novel zinc finger protein, is an inhibitor of tumor necrosis factor-induced apoptosis. The mechanism by which A20 exerts its protective effect is currently unknown. Several isoforms of the 14-3-3 proteins were found to interact with A20 in a yeast two-hybrid screen. A20 bound several 14-3-3 isoforms in vitro. Moreover, transfected A20 was found to preferentially bind the endogenous eta14-3-3 isoform, whereas the beta/zeta isoforms co-immunoprecipitated much less efficiently, and epsilon14-3-3 had an intermediate affinity. Importantly, c-Raf, a previously described 14-3-3-interacting protein, also preferentially bound the eta isoform. The cellular localization and subcellular fractionation of A20 was dramatically altered by co-transfected 14-3-3, providing the first experimental evidence for the notion that 14-3-3 can function as a chaperone. Furthermore, c-Raf and A20 co-immunoprecipitated in a 14-3-3-dependent manner, suggesting that 14-3-3 can function as a bridging or adapter molecule.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: C
authors.initials: C
authors.lastname: Vincenz
authors.forename: V M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins; D006801:Humans; D007158:Immunologic Techniques; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction; D012995:Solubility; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014446:Tyrosine 3-Monooxygenase; D016335:Zinc Fingers
chemical_list: D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D010455:Peptides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3