Hypoxic regulation of stability of connective tissue growth factor/CCN2 mRNA by 3′-untranslated region interacting with a cellular protein in human chondrosarcoma cells

S. Kondo, S. Kubota, Y. Mukudai, N. Moritani, T. Nishida, H. Matsushita, S. Matsumoto, T. Sugahara, M. Takigawa

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Connective tissue growth factor (CTGF/CCN2) can be induced by various forms of stress such as exposure to high glucose, mechanical load, or hypoxia. Here, we investigated the molecular mechanism involved in the induction of ctgf/ccn2 by hypoxia in a human chondrosarcoma cell line, HCS-2/8. Hypoxia increased the ctgf/ ccn2 mRNA level by altering the 3′-untranslated region (UTR)-mediated mRNA stability without requiring de novo protein synthesis. After a series of extensive analyses, we eventually found that the cis-repressive element of 84 bases within the 3′-UTR specifically bound to a cytoplasmic/nuclear protein. By conducting a UV crosslinking assay, we found the cytoplasmic/nuclear protein to be a 35 kDa molecule that bound to the cis-element in a hypoxia-inducible manner. These results suggest that a cis-element in the 3′-UTR of ctgf/ccn2 mRNA and trans-factor counterpart(s) play an important role in the post-transcriptional regulation by determining the stability of ctgf/ccn2 mRNA.

Original languageEnglish
Pages (from-to)1099-1110
Number of pages12
JournalOncogene
Volume25
Issue number7
DOIs
Publication statusPublished - Feb 16 2006

Keywords

  • 3′-UTR
  • CCN family
  • Connective tissue growth factor
  • Hypoxia
  • Post-transcriptional regulation
  • mRNA stability

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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