A splice variant of ADAMTS13 is expressed in human hepatic stellate cells and cancerous tissues

Thromb Haemost. 2010 Sep;104(3):531-5. doi: 10.1160/TH09-12-0860. Epub 2010 Jul 20.

Abstract

Although ADAMTS13, the von Willebrand factor (VWF)-cleaving protease, is expressed in a range of tissues, the physiological significance of tissue-specific ADAMTS13 alternative splicing isoforms have yet to be clarified. Screening a panel of human tissues and cell lines revealed a spliced ADAMTS13 transcript in hepatic stellate cells and a hepatoma cell line that retains the 25th intron. A nonsense codon within the intron truncates the protease, which gains 64 novel amino acids in lieu of both CUB domains. This isoform, while retaining VWF-cleaving capability, accumulates intracellularly and its biological inaccessibility may prevent its participation in regulating haemostasis and other physiologic functions.

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • ADAMTS13 Protein
  • Alternative Splicing
  • Animals
  • CHO Cells
  • Carcinoma, Hepatocellular / enzymology*
  • Cell Line, Tumor
  • Codon, Nonsense
  • Cricetinae
  • Cricetulus
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Hepatic Stellate Cells / enzymology*
  • Humans
  • Introns
  • Liver Neoplasms / enzymology*
  • Protein Isoforms
  • RNA, Messenger / metabolism
  • Substrate Specificity
  • Transfection
  • von Willebrand Factor / metabolism

Substances

  • Codon, Nonsense
  • Protein Isoforms
  • RNA, Messenger
  • von Willebrand Factor
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human