Alternative splicing of human NT5E in cirrhosis and hepatocellular carcinoma produces a negative regulator of ecto-5'-nucleotidase (CD73).
Bottom Line: The two human isoforms exhibited functional differences, such that ectopic expression of canonical CD73 (CD73L) in human HepG2 cells was associated with decreased expression of the proliferation marker Ki67, whereas CD73S expression did not have an effect on Ki67 expression.Furthermore, CD73S complexed with CD73L and promoted proteasome-dependent CD73L degradation.The findings reveal species-specific CD73 regulation, with potential significance to cancer, fibrosis, and other diseases characterized by changes in CD73 expression and function.
Affiliation: Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.Show MeSH
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Mentions: We also assessed the expression of a putative mouse protein (Uniprot ID Q8C8G9) that shares some sequence similarity to human CD73S (Figure 4A). Despite robust mRNA detection upon overexpression of the corresponding cDNA in primary mouse hepatocytes, we did not detect any protein (Figure 4, B and C). Using a different cell host (BHK-21 cells), addition of a proteasome inhibitor and analysis of the cell culture medium also did not reveal protein expression in the cells or the culture medium (unpublished data), suggesting that CD73S is a human-specific variant.
Affiliation: Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.