title: MIP-T3, a novel protein linking tumor necrosis factor receptor-associated factor 3 to the microtubule network.
abstract: In this study, we report the identification of a novel tumor necrosis factor receptor-associated factor 3 (TRAF3)-interacting protein designated MIP-T3. MIP-T3 is a 83-kDa protein with no significant homology to known mammalian proteins. MIP-T3 mRNA and TRAF3 mRNA are ubiquitously expressed, and TRAF3 is the only TRAF protein to interact with MIP-T3. The MIP-T3-TRAF3 interaction requires the coiled-coil TRAF-N domain of TRAF3. To our knowledge, this is the first case of a TRAF-binding protein that interacts with a single member of the TRAF family specifically through a TRAF-N coiled-coil domain. MIP-T3 binds to Taxol-stabilized microtubules and to tubulin in vitro, and MIP-T3 recruits TRAF3 to microtubules when both proteins are overexpressed in HeLa cells. In a 293 cell line stably expressing CD40, TRAF3 is released from the TRAF3.MIP-T3 complex and recruited to the CD40 receptor upon CD40 ligand stimulation. MIP-T3 may provide a novel mechanism in sequestering TRAF3 to the cytoskeletal network.
authors.affiliation: Tularik Inc., South San Francisco, California 94080, USA. ling@tularik.com
authors.forename: L
authors.initials: L
authors.lastname: Ling
authors.forename: D V
authors.initials: DV
authors.lastname: Goeddel
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D017239:Paclitaxel / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D017384:Sequence Deletion; D048008:TNF Receptor-Associated Factor 3; D020798:Two-Hybrid System Techniques
chemical_list: D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D048008:TNF Receptor-Associated Factor 3; C412724:TRAF3IP1 protein, human; D023201:CD40 Ligand; D017239:Paclitaxel