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Galectin-3-binding protein inhibits extracellular heparan 6-O-endosulfatse Sulf-2.


ABSTRACT: Human extracellular 6-O-endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6-O sulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). In spite of its importance, limited information is available on direct protein-protein interactions of the Sulf-2 protein in the tumor microenvironment. In this study, we used monoclonal antibody (mAb) affinity purification and mass spectrometry to identify galectin-3-binding protein (LG3BP) as a highly specific binding partner of Sulf-2 in the secretome of HNSCC cell lines. We validated their direct interaction in vitro using recombinant proteins and have shown that the chondroitin sulfate (CS) covalently bound to the Sulf-2 influences the binding to LG3BP. We confirmed importance of the CS chain for the interaction by generating a mutant Sulf-2 protein that lacks the CS. Importantly, we have shown that the LG3BP inhibits Sulf-2 activity in vitro in a concentration dependent manner. As a consequence, the addition of LG3BP to a spheroid cell culture inhibited invasion of the HNSCC cells into Matrigel. Thus, Sulf-2 interaction with LG3BP has functional relevance, and may regulate physiological activity of the Sulf-2 enzyme as well as its activity in the tumor microenvironment.

SUBMITTER: Panigrahi A 

PROVIDER: S-EPMC10769223 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Galectin-3-binding protein inhibits extracellular heparan 6-<i>O</i>-endosulfatse Sulf-2.

Panigrahi Aswini A   Benicky Julius J   Aljuhani Reem R   Mukherjee Pritha P   Nováková Zora Z   Bařinka Cyril C   Goldman Radoslav R  

bioRxiv : the preprint server for biology 20231221


Human extracellular 6-<i>O</i>-endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6-<i>O</i> sulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). In spite of its importance, limited information is available on direct prote  ...[more]

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