RGD peptides released from βig-h3, a TGF-β-induced cell-adhesive molecule, mediate apoptosis

Jung Eun Kim, Song Ja Kim, Ha Won Jeong, Byung Heon Lee, Je Yong Choi, Rang Woon Park, Jae Yong Park, In San Kim

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84 Citations (Scopus)

Abstract

βig-h3 is a transforming growth factor-β (TGF-β)-induced cell-adhesive molecule and has an RGD sequence at its C-terminus. A previous report suggested that βig-h3 normally undergoes carboxy-terminal processing that results in the loss of the RGD sequence. RGD peptides appear to play various roles in cell function. Here we show that the RGD peptides released from βig-h3 may facilitate TGF-β-induced apoptosis. We found that carboxy-terminal cleavage of βig-h3 occurred after its secretion, and that overexpression of the wild-type βig-h3 induced apoptosis, unlike the C-terminal deleted but RGD-containing mutant βig-h3, which is resistant to C-terminal processing. The βig-h3-induced apoptosis was abolished by either deletion of the RGD sequence or mutation of RGD to RAE. Synthetic peptides of ERGDEL and GRGDSP derived from βig-h3 and fibronectin, respectively, also induced apoptosis, unlike ERGEEL and GRGESP. Culture supernatants of cells overexpressing βig-h3 filtered to isolate molecules smaller than 3 kDa also induced apoptosis. A fusion protein composed of the N-terminal 100 amino acids of fibronectin and the RGD-containing C-terminal part of βig-h3 was also subjected to C-terminal cleavage and overexpression resulted in apoptosis. The anti-βig-h3 antibody blocks TGF-β-induced apoptosis. Thus, βig-h3 may be important in regulating cell apoptosis by providing soluble RGD peptides.

Original languageEnglish
Pages (from-to)2045-2053
Number of pages9
JournalOncogene
Volume22
Issue number13
DOIs
Publication statusPublished - 2003 Apr 3

Keywords

  • Anoikis
  • Apoptosis
  • Cell adhesion
  • RGD peptide
  • TGF-β
  • βig-h3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Kim, J. E., Kim, S. J., Jeong, H. W., Lee, B. H., Choi, J. Y., Park, R. W., Park, J. Y., & Kim, I. S. (2003). RGD peptides released from βig-h3, a TGF-β-induced cell-adhesive molecule, mediate apoptosis. Oncogene, 22(13), 2045-2053. https://doi.org/10.1038/sj.onc.1206269