Journal
CELL DEATH AND DIFFERENTIATION
Volume 17, Issue 8, Pages 1277-1287Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2010.8
Keywords
c-Abl; Arg; Galectin-3; autophagy; apoptosis
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Funding
- Natural Science Foundation of China [30730027, 3027316]
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Galectin-3 (Gal3) has important roles in tumor transformation and metastasis. This study shows that c-Abl and Abl-related gene (Arg) associate with and phosphorylate Gal3. The SH (Src homology) 3 domains of c-Abl/Arg bind to a P(80)GPPSGP motif of Gal3, and Tyr79 and Tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of Gal3. Cells expressing Gal3 and treated with the c-Abl/Arg inhibitor STI571, Gal3-depleted cells, and Gal3-depleted cells expressing Gal3 phosphorylation mutants all display an increased sensitivity to apoptosis-inducing agents. In addition, tumor cells expressing the phosphorylation mutants show impaired tumorigenicity. These results partially explain the antiapoptotic effect of Abl and Arg. As tumors frequently overexpress Gal3, a c-Abl/Arg-specific inhibitor may potentially be applied along with other antitumor drugs to target the lysosomal degradation of Gal3 in tumor therapy. Cell Death and Differentiation (2010) 17, 1277-1287; doi:10.1038/cdd.2010.8; published online 12 February 2010
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