Regulatory Mechanisms of FUT8 Activity and Expression in Cells

FUT8 is a glycosyltransferase which transfers fucose to N-glycans to make the core fucose. Core fucosylation has been implicated in the development of chronic obstructive pulmonary disease (COPD), melanoma metastasis, and the severity of coronavirus disease 2019 (COVID-19), and it also serves as a basis for diagnostic markers in liver cancer. The enzymatic activity and subcellular localization of FUT8 are closely linked to the expression levels of core fucose, yet the regulatory mechanisms remain poorly understood. Recently, through functional analyses of the non-catalytic SH3 domain and the stem region, we elucidated mechanisms covering FUT8 activity and stability. Furthermore, we identified the proteases SPP and SPPL3 as mediators of FUT8 cleavage and secretion, and revealed that secreted FUT8 shows different substrate selectivity from the membrane-bound form. These findings provide new perspectives on the regulation of glycosylation and important insights into the functional control of glycosyltransferases.