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

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

Cellular signalling

Xiaojun Sun, Yinyin Wang, Shigao Yang, Fangli Ren, Yongjing Xia, Zhijie Chang

Affiliations

  1. State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China.

PMID: 23770285 DOI: 10.1016/j.cellsig.2013.06.006

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

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

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