Cleavage and phosphorylation: important post-translational modifications of galectin-3

As the unique chimeric member of the β-galactoside-binding protein family, galectin-3 is a multivalent and multifunctional oncogenic protein involved in multiple physiological and pathological processes, including cell growth, cell differentiation, cell adhesion, RNA splicing, cell apoptosis, and malignant transformation. Post-translational modifications can effectively increase a protein’s functional diversity, either by degradation or adding chemical modifications, thus regulating activity, localization, and ligand interaction. In order to clearly understand the functional mechanisms of galectin-3 involved in normal cell biology and pathogenesis, here, we have summarized the previously reported post-translational modifications of galectin-3, including cleavage and phosphorylation. Cleavage of galectin-3 by MMPs, PSA, and proteases from parasites generated intact carbohydrate-recognition domain and N-terminal peptides of varying lengths that retained lectin binding activity but lost multivalence. Serine and tyrosine phosphorylation of galectin-3 by c-Abl, CKI, and GSK-3β could regulate its localization and associated signal transduction. Accordingly, cleavage and phosphorylation play an important role in regulating galectin-3 function via altering its multivalence, localization, and ligand interaction.