Apoptotic signaling by TNFR1 is inhibited by the α2-6 sialylation, but not α2-3 sialylation, of the TNFR1 N-glycans.

ABSTRACT: The TNF-TNFR1 signaling pathway plays a pivotal role in regulating the balance between cell survival and cell death. Upon binding to TNF, plasma membrane-localized TNFR1 initiates survival signaling, whereas TNFR1 internalization promotes caspase-mediated apoptosis. We previously reported that the α2-6 sialylation of TNFR1 by the tumor-associated sialyltransferase ST6GAL1 diverts signaling toward survival by inhibiting TNFR1 internalization. In the current investigation, we interrogated the mechanisms underlying sialylation-dependent regulation of TNFR1 and uncovered a novel role for α2-6 sialylation, but not α2-3 sialylation, in mediating apoptosis-resistance. Our studies utilized HEK293 cells with deletion of sialyltransferases that modify N-glycans with either α2-3-linked sialic acids (

SUBMITTER: Hwang J 

PROVIDER: S-EPMC11732462 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature