Translocation of HSP27 into liver cancer cell nucleus may be associated             with phosphorylation and O-GlcNAc glycosylation.
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.
Liver Cancer Institute, Zhongshan Hospital, and Research Center for Cancer, Institute of Biomedical Science, Fudan University, Shanghai 200032, PR China.
Kun
K
Guo
Lin
L
Gan
Shu
S
Zhang
Feng Jie
FJ
Cui
Wang
W
Cun
Yan
Y
Li
Nan Xiao
NX
Kang
Mei Dong
MD
Gao
Kun Yin
KY
Liu
D000117:Acetylglucosamine / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones; D010766:Phosphorylation; D014162:Transfection
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D000117:Acetylglucosamine