The resilience of cancer-specific protein galectin-3: Implications in biological functions
Department of Chemistry
Structural degradation is detrimental for protein activity and functions. We recently found that the tumor-associated protein galectin-3 (Gal-3) is apparently an exception to this rule. Gal-3 plays important roles in cancer but its functions are not fully understood. We have found that the affinity purified Gal-3, when stored with lactose at 4°C for more than six weeks, undergoes complete degradation even in the absence of collagenases. Full-length Gal-3 after full degradation produced a single protein band of 17 kDa. This molecular weight is similar to that of the CRD (carbohydrate recognition domain) portion of Gal-3. Conventionally, the CRD is separated from intact Gal-3 by enzymatic digestion using collagenases. However, in the present case, Gal-3 apparently self-degraded to produce the CRD without the catalytic action of collagenases. Our data indicate that degradation of Gal-3 significantly alters the protein but the CRD remains intact and functionally active. Like the full-length Gal-3, the CRDs interacted with thyroglobulin, chondroitin sulfate A and C. However, the CRDs could not cross-link these multivalent ligands as revealed by our spectroscopic analysis. Our current observations suggest that Gal-3 retains it ligand recognition properties even when it is substantially degraded in a challenging cellular environment. Thus the degraded Gal-3 can still carry out some of the functions of intact Gal-3. Although the CRDs retain the binding property of its intact precursor (Gal-3), they lose the ability to cross-link cellular receptors. As a result, the CRDs generated through degradation may influence cell signaling by competing with intact Gal-3 for the same receptors in cellular environment.
Biochemistry and Molecular Biology
Dam, T. K.,
Kadav, P. D.,
The resilience of cancer-specific protein galectin-3: Implications in biological functions.
Biochemistry and Molecular Biology,
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/15802