Document Detail

Transforming growth factor beta1 signaling via interaction with cell surface Hyal-2 and recruitment of WWOX/WOX1.
MedLine Citation:
PMID:  19366691     Owner:  NLM     Status:  MEDLINE    
Transforming growth factor beta (TGF-beta) initiates multiple signal pathways and activates many downstream kinases. Here, we determined that TGF-beta1 bound cell surface hyaluronidase Hyal-2 on microvilli in type II TGF-beta receptor-deficient HCT116 cells, as determined by immunoelectron microscopy. This binding resulted in recruitment of proapoptotic WOX1 (also named WWOX or FOR) and formation of Hyal-2.WOX1 complexes for relocation to the nuclei. TGF-beta1 strengthened the binding of the catalytic domain of Hyal-2 with the N-terminal Tyr-33-phosphorylated WW domain of WOX1, as determined by time lapse fluorescence resonance energy transfer analysis in live cells, co-immunoprecipitation, and yeast two-hybrid domain/domain mapping. In promoter activation assay, ectopic WOX1 or Hyal-2 alone increased the promoter activity driven by Smad. In combination, WOX1 and Hyal-2 dramatically enhanced the promoter activation (8-9-fold increases), which subsequently led to cell death (>95% of promoter-activated cells). TGF-beta1 supports L929 fibroblast growth. In contrast, transiently overexpressed WOX1 and Hyal-2 sensitized L929 to TGF-beta1-induced apoptosis. Together, TGF-beta1 invokes a novel signaling by engaging cell surface Hyal-2 and recruiting WOX1 for regulating the activation of Smad-driven promoter, thereby controlling cell growth and death.
Li-Jin Hsu; Lori Schultz; Qunying Hong; Kris Van Moer; John Heath; Meng-Yen Li; Feng-Jie Lai; Sing-Ru Lin; Ming-Hui Lee; Cheng-Peng Lo; Yee-Shin Lin; Shur-Tzu Chen; Nan-Shan Chang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-04-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-01     Completed Date:  2009-07-13     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16049-59     Citation Subset:  IM    
Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
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MeSH Terms
Cell Adhesion Molecules / genetics,  physiology*
Cell Membrane / physiology*
Colorectal Neoplasms
DNA Primers
Fluorescence Resonance Energy Transfer
GPI-Linked Proteins
Gene Expression Regulation
HCT116 Cells
Hyaluronoglucosaminidase / genetics,  physiology*
L Cells (Cell Line)
Oxidoreductases / physiology*
Promoter Regions, Genetic
Protein-Serine-Threonine Kinases / deficiency,  physiology*
Receptors, Transforming Growth Factor beta / deficiency,  physiology*
Tumor Suppressor Proteins / physiology*
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/DNA Primers; 0/GPI-Linked Proteins; 0/Receptors, Transforming Growth Factor beta; 0/Tumor Suppressor Proteins; EC 1.-/Oxidoreductases; EC 1.1.1.-/WWOX protein, human; EC type I receptor; EC Kinases; EC growth factor-beta type II receptor; EC protein, human; EC

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