title: Activation of TAK1 by Sef-S induces apoptosis in 293T cells.
abstract: Sef (similar expression to fgf genes, also named IL-17RD) was identified as a negative regulator of fibroblast growth factor signaling. Sef-S, an alternative splice isoform of Sef, inhibits FGF-induced NIH3T3 cell proliferation. Here we report that Sef-S physically interacts with TAK1, induces Lys63-linked TAK1 polyubiquitination on lysine 209 and TAK1-mediated JNK and p38 activation. Co-overexpression of TAK1 WT, K34R, K150R, K158R mutants with Sef-S induces Lys63-linked TAK1 polyubiquitination whereas TAK1 K63R and K209R mutants fail. Furthermore, co-overexpression of Sef-S and TAK1 induce 293T cells apoptosis. These results reveal Sef-S actives Lys63-linked TAK1 polyubiquitination on lysine 209, induces TAK1-mediated JNK and p38 activation and also results apoptosis in 293T cells.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Sun
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Wang
authors.forename: Shigao
authors.initials: S
authors.lastname: Yang
authors.forename: Fangli
authors.initials: F
authors.lastname: Ren
authors.forename: Yongjing
authors.initials: Y
authors.lastname: Xia
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D015398:Signal Transduction; D054875:Ubiquitination / Q000235:genetics; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020381:Interleukin-17; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D000099151:MAP Kinase Kinase Kinase 7; C464462:IL17D protein, human
keywords: Apoptosis; Erk1/2; FBS; FGF; IgG; JNK; MAPK; SPRED; Sef; Sprouty-related EVH1-domain containing; Ub; fetal bovine serum; fibroblast growth factor; immunoglobulin G; nubiquitination; p38; ubiquitin; wild type; wt