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

Noam Shomron; Nobuko Hamasaki-Katagiri; Ryan Hunt; Klilah Hershko; Elie Pommier; S. Geetha; Adam Blaisdell; Andrew Marple; Isabella Roma; Jordan Newell; Courtni Allen; Scott Friedman; Chava Kimchi-Sarfaty

doi:10.1160/TH09-12-0860

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(03): 531-533
DOI: 10.1160/TH09-12-0860

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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

Noam Shomron^#

¹Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

,

Nobuko Hamasaki-Katagiri^#

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

,

Ryan Hunt

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

,

Klilah Hershko

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

,

Elie Pommier

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

,

S. Geetha

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

,

Adam Blaisdell

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

,

Andrew Marple

³Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

,

Isabella Roma

³Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

,

Jordan Newell

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

,

Courtni Allen

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

,

Scott Friedman

⁴Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York, USA

,

Chava Kimchi-Sarfaty

²Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA

› Author Affiliations

Abstract

Summary

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 25^th 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.

Keywords

ADAMTS13 - alternative splicing - intron retention - TTP - CUB domain

Full Text

References

References
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