Abstract
Abstract N-linked glycosylation is a critical determinant of protein structure and function, regulating processes such as protein folding, stability, localization, ligand-receptor binding and intracellular signaling. The type II TGF-β receptor (TβRII) plays a crucial role in the TGF-β signaling pathway. Although N-linked glycosylation of TβRII was first demonstrated over a decade ago, it is unclear how this modification affects TβRII biology. By generating deficient N-linked glycosylation (dNG) mutants, in which each asparagine was converted to glutamine, we show here that N-linked glycosylation occurs on two conserved asparagine residues in the extracellular domain of TβRII. dNG mutant TbRII lines indeed exhibited defective N-linked glycosylation. Notably, non-glycosylated TβRII was more sensitive to proteasome-mediated degradation than fully N-glycosylated TβRII, suggesting that the N-linked glycosylation protects TβRII from proteasome-mediated degradation. Defective N-linked glycosylation also induced TβRII to accumulate in the endoplasmic reticulum (ER), resulting in decreased expression on the cell surface compared to N-glycosylated TβRII. Ultimately, upon TGF-β stimulation, cells expressing dNG mutant TβRII lines were not efficiently able to activate downstream signaling due to the decreased number of cell surface-expressed receptor molecules. These findings demonstrate that N-linked glycosylation is essentially required for the stability and cell surface localization of TβRII. Moreover, by comparing the N-linked glycosylation levels of TβRII in various cancer cell lines, we suggest that the degree of N-linked glycosylation of TβRII might be one of molecular mechanisms involved in the different cellular responses of cancer cell lines upon TGF-β treatment, shedding light on the N-linked glycosylation that fosters TGF-β resistance in many cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1977. doi:10.1158/1538-7445.AM2011-1977
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have