Premium
TIAF1 physically heterodimerizes with WOX1 in the mitochondria: a role in apoptosis
Author(s) -
Chang NanShan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.617.1
Subject(s) - programmed cell death , gene knockdown , apoptosis , microbiology and biotechnology , biology , mitochondrion , cell growth , cell , cancer cell , biochemistry , cancer , genetics
Overexpressed TIAF1 (TGF‐beta1‐induced antiapoptotic factor) promotes the growth of fibroblasts, but induces apoptosis in monocytic and non‐fibroblast cells. Functional property of TIAF1 in regulating cell growth and death is largely unknown. Here, we show that knockdown of endogenous TIAF1 by siRNA prevented cell growth inhibition and apoptosis by staurosporine, tumor necrosis factor, UV light, and TGF‐beta1. We have shown that overexpressed tumor suppressor WOX1 (WWOX or FOR) induced cell death at the mitochondrial level. Interestingly, WOX1 induced‐growth suppression and death of fibroblasts and prostate cancer cells was blocked in TIAF1‐knockdown cells. Analysis by fluorescence resonance energy transfer (FRET) and co‐immunoprecipitation revealed that TIAF1 physically heterodimerizes with WOX1 to its C‐terminus (designated D3 region). WOX2, an isoform of WOX1, possesses a truncated C‐terminus and did not bind TIAF1. Time‐lapse microscopy revealed that UV light induced an initial increased in the heterodimerization, followed by dissociation between WOX1 and TIAF1. Overexpressed WOX1 and TIAF1 caused apoptosis synergistically, suggesting their role in programmed cell death via the mitochondrial pathway.