Activation of TAK1 by Sef-S induces apoptosis in 293T cells

Cell Signal. 2013 Oct;25(10):2039-46. doi: 10.1016/j.cellsig.2013.06.006. Epub 2013 Jun 11.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • Apoptosis / genetics*
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Mice
  • NF-kappa B / metabolism
  • NIH 3T3 Cells
  • Phosphorylation
  • Signal Transduction*
  • Ubiquitination / genetics

Substances

  • IL17D protein, human
  • Interleukin-17
  • NF-kappa B
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7