Protein sialylation by sialyltransferase involves radiation resistance.
Previously, we identified beta-galactoside alpha(2,6)-sialyltransferase (ST6Gal I) as a candidate biomarker for ionizing radiation. The expression of ST6Gal I and the level of protein sialylation increased following radiation exposure in a dose-dependent manner. Radiation induced ST6Gal I cleavage and the cleaved form of ST6Gal I was soluble and secreted. Sialylation of integrin beta1, a glycosylated cell surface protein, was stimulated by radiation exposure and this increased its stability. Overexpression of ST6Gal I in SW480 colon cancer cells that initially showed a low level of ST6Gal I expression increased the sialylation of integrin beta1 and also increased the stability of the protein. Inhibition of sialylation by transfection with neuraminidase 2 or neuraminidase 3 or by treatment with short interfering RNA targeting ST6Gal I reversed the effects of ST6Gal I overexpression. In addition, ST6Gal I overexpression increased clonogenic survival following radiation exposure and reduced radiation-induced cell death and caspase 3 activation. However, removal of sialic acids by neuraminidase 2 or knockdown of expression by short interfering RNA targeting ST6Gal I restored radiation-induced cell death phenotypes. In conclusion, radiation exposure was found to increase the sialylation of glycoproteins such as integrin beta1 by inducing the expression of ST6Gal I, and increased protein sialylation contributed to cellular radiation resistance.
Lee
Minyoung
M
Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Lee
Hae-June
HJ
Bae
Sangwoo
S
Lee
Yun-Sil
YS
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance / Q000528:radiation effects; D011839:Radiation, Ionizing; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D012995:Solubility / Q000528:radiation effects; D013816:Thermodynamics; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D006023:Glycoproteins; D019012:Integrin beta1; D012794:Sialic Acids; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase