Translocation of HSP27 into liver cancer cell nucleus may be associated with phosphorylation and O-GlcNAc glycosylation
Translocation of HSP27 into liver cancer cell nucleus may be associated with phosphorylation and O-GlcNAc glycosylation
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HSP27易位至肝癌细胞核可能与磷酸化和O-GlcNAc糖基化有关
DOI：
10.3892/or.2012.1844
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发表时间：
2012-08-01
期刊：
影响因子：
4.2
通讯作者：
Liu, Kun Yin
中科院分区：
文献类型：
--
作者：
Guo, Kun;Gan, Lin;Liu, Kun Yin
据报道，O-GlcN酰化和O-磷酸化之间的动态相互作用负责改变热休克蛋白的活性或定位。本研究的目的是确定肝细胞癌细胞中HSP27的O-GlcN酰化和O-磷酸化之间的动态相互作用是否影响其进入细胞核。我们通过用编码野生型HSP27(HSP27-WT)、其非磷酸化(HSP27-3A)和假磷酸化(HSP27-3D)突变体的质粒转染肝癌细胞，证明了HSP27进入细胞核与其磷酸化相关，然而，并不是所有内源或外源核HSP27都被磷酸化修饰。我们在肝癌细胞中观察到HSP27被O-GlcNAc糖基化修饰，并报道在HSP27保守的Ser残基上，可以用YinOYang 1.2方法预测交替的磷酸化和O-GlcNAc修饰。此外，P79350或SB203580联合PUGNAc处理后，HSP27-WT和HSP27-3D的核进口增加，提示HSP27进入细胞核不仅与磷酸化有关，而且与O-GlcNAc糖基化有关。总之，肝癌细胞中HSP27的O-GlcN酰化可能是HSP27功能的一种新的调节方式，尤其是它进入细胞核的方式。HSP27的糖基化和磷酸化之间的串扰或相互作用可以调节其在肝癌中的亚细胞定位和生物学功能。
It has been reported that the dynamic interplay between O-GlcNAcylation and O-phosphorylation is responsible for altering the activity or localization of heat-shock proteins. The aim of this study was to determine whether dynamic interplay between O-GlcNAcylation and O-phosphorylation of HSP27 in hepatocellular cancer (HCC) cells affect its entry into the nucleus. We demonstrate that the entry of HSP27 into the nucleus correlated with its phosphorylation through transfecting HCC cells with plasmids coding for wild-type HSP27 (HSP27-WT), its non-phosphorylatable (HSP27-3A) and pseudophosphorylated (HSP27-3D) mutants, however, not all of the endogenous or exogenous nuclear HSP27 was modified by phosphorylation. We observed that HSP27 was modified with O-GlcNAc glycosylation in HCC cells and report that at conserved Ser residues of HSP27, alternative phosphorylation and O-GlcNAc modification can be predicted by the YinOYang 1.2 method. Furthermore, after P79350 or combined SB203580 and PUGNAc treatment, increased nuclear import of HSP27-WT and HSP27-3D implied that the entry of HSP27 into the nucleus was not only correlated with phosphorylation, but also with O-GlcNAc glycosylation. Collectively, O-GlcNAcylation of HSP27 in HCC cells may be a novel regulatory mode of HSP27 function, particularly for its entry into the nucleus. Crosstalk or interplay between glycosylation and phosphorylation of HSP27 could regulate its subcellular localization and biological functions in liver cancer.