O-linked-β-N-acetylglucosamine(O-GlcNAc)glycosylation(O-GlcNAcylation)and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenes...O-linked-β-N-acetylglucosamine(O-GlcNAc)glycosylation(O-GlcNAcylation)and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.However,a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma(HB),a highly malignant primary hepatic tumor with an extremely low incidence in children,has not been performed.Here,we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.Our results identified 114 O-GlcNAcylated peptides belonging to 78 proteins and 3494 phosphorylated peptides in 2088 proteins.Interestingly,41 proteins were modified by both O-GlcNAcylation and phosphorylation.These proteins are involved in multiple molecular and cellular processes,including chromatin remodeling,transcription,translation,transportation,and organelle organization.In addition,we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1.Further,O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.Collectively,our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.展开更多
基金This study was financially supported by the National Natural Science Foundation of China(81572330,81802103,81772941 and 81871727)a Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines in Shanghai(2017BR036)+2 种基金the Program of Shanghai Academic/Technology Research Leaders(18XD1402600)Shanghai Municipal Education Commission-Gaofeng Clinical Medi-cine Grant Support(20171926)the Science and Technology Development Fund of the Pudong New Area of Shanghai(PKJ2017-Y03).
文摘O-linked-β-N-acetylglucosamine(O-GlcNAc)glycosylation(O-GlcNAcylation)and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.However,a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma(HB),a highly malignant primary hepatic tumor with an extremely low incidence in children,has not been performed.Here,we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.Our results identified 114 O-GlcNAcylated peptides belonging to 78 proteins and 3494 phosphorylated peptides in 2088 proteins.Interestingly,41 proteins were modified by both O-GlcNAcylation and phosphorylation.These proteins are involved in multiple molecular and cellular processes,including chromatin remodeling,transcription,translation,transportation,and organelle organization.In addition,we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1.Further,O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.Collectively,our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.
