A splice variant of ADAMTS13 is expressed in human hepatic stellate cells and cancerous tissues.
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.
Shomron
Noam
N
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Hamasaki-Katagiri
Nobuko
N
Hunt
Ryan
R
Hershko
Klilah
K
Pommier
Elie
E
Geetha
S
S
Blaisdell
Adam
A
Dobkin
Alexandra
A
Marple
Andrew
A
Roma
Isabella
I
Newell
Jordan
J
Allen
Courtni
C
Friedman
Scott
S
Kimchi-Sarfaty
Chava
C
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D017398:Alternative Splicing; D000818:Animals; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D045744:Cell Line, Tumor; D018389:Codon, Nonsense; D006224:Cricetinae; D003412:Cricetulus; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055166:Hepatic Stellate Cells / Q000201:enzymology*; D006801:Humans; D007438:Introns; D008113:Liver Neoplasms / Q000201:enzymology*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection; D014841:von Willebrand Factor / Q000378:metabolism
D018389:Codon, Nonsense; D020033:Protein Isoforms; D012333:RNA, Messenger; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human