title: Physical and functional interaction of filamin (actin-binding protein-280) and tumor necrosis factor receptor-associated factor 2.
abstract: Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is an intracellular protein involved in signal transduction from TNF receptor I and II and related receptors. TRAF2 is required for TNF-induced activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), and TRAF2 can also mediate activation of NF-kappaB. Here we have identified the actin-binding protein Filamin (actin-binding protein-280) as a TRAF2-interacting protein. Filamin binds to the Ring zinc finger domain of TRAF2. Overexpressed Filamin inhibits TRAF2-induced activation of JNK/SAPK and of NF-kappaB. Furthermore, ectopically expressed Filamin inhibits NF-kappaB activation induced via TNF, interleukin-1, Toll receptors, and TRAF6 but not activation induced via overexpression of NIK, a downstream effector in these pathways. Importantly, TNF fails to activate SAPK or NF-kappaB in a human melanoma cell line deficient in Filamin. Reintroduction of Filamin into these cells restores the TNF response. The data imply a role for Filamin in inflammatory signal transduction pathways.
authors.affiliation: Immune Activation Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
authors.forename: A
authors.initials: A
authors.lastname: Leonardi
authors.forename: H
authors.initials: H
authors.lastname: Ellinger-Ziegelbauer
authors.forename: G
authors.initials: G
authors.lastname: Franzoso
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: U
authors.initials: U
authors.lastname: Siebenlist
mesh_terms: D001665:Binding Sites; D003285:Contractile Proteins / Q000378:metabolism*; D064448:Filamins; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008840:Microfilament Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2; D048029:TNF Receptor-Associated Factor 6; D016335:Zinc Fingers; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D048031:JNK Mitogen-Activated Protein Kinases; D008840:Microfilament Proteins; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047992:TNF Receptor-Associated Factor 2; D048029:TNF Receptor-Associated Factor 6; D000097782:NF-kappaB-Inducing Kinase; C578661:FLNC protein, human