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: To determine whether CD73S and CD73L exhibit functional differences, we transfected each isoform into HepG2 cells and monitored the expression of the cell proliferation marker Ki67. The cells expressing CD73L had a significant decrease in Ki67 staining, whereas CD73S expression did not significantly alter Ki67 expression relative to neighboring untransfected cells (Figure 5, A and B). Therefore CD73L and CD73S exhibit functional differences with respect to their ability to modulate the proliferation potential of cultured human HCC cells.
Affiliation: Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.