title: FBXW10 is negatively regulated in transcription and expression level by protein O-GlcNAcylation.
abstract: Intricate cross-talks exist among multiple post-translational modifications that play critical roles in various cellular events, such as the control of gene expression and regulation of protein function. Here, the cross-talk between O-GlcNAcylation and ubiquitination was investigated in HEK293T cells. By PCR array, 84 ubiquitination-related genes were explored in transcription level in response to the elevation of total protein O-GlcNAcylation due to over-expression of OGT, inhibition of OGA or GlcN treatment. Varied genes were transcriptionally regulated by using different method. But FBXW10, an F-box protein targeting specific proteins for ubiquitination, could be negatively regulated in all ways, suggesting its regulation by protein O-GlcNAcylation. By RT-PCR and Western blot analysis, it was found that FBXW10 could be sharply down-regulated in mRNA and protein level in GlcN-treated cells in a time-dependent way, in line with the enhancement of protein O-GlcNAcylation. It was also found that endogenous FBXW10 was modified by O-GlcNAc in HEK293T cells, implying O-GlcNAcylation might regulate FBXW10 in multiple levels. These findings indicate that O-GlcNAcylation is involved in the regulation of ubiquitination-related genes, and help us understand the cross-talk between O-GlcNAcylation and ubiquitination.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Hui
authors.forename: Li
authors.initials: L
authors.lastname: Ling
authors.forename: Liu
authors.initials: L
authors.lastname: Xiaoyan
authors.forename: Wang
authors.initials: W
authors.lastname: Yuqiu
authors.forename: Wang
authors.initials: W
authors.lastname: Peng
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lianwen
mesh_terms: D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D010957:Plasmids; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000737:chemistry; D054875:Ubiquitination
chemical_list: D044783:F-Box Proteins; C574378:FBXW10 protein, human; D012333:RNA, Messenger; D025801:Ubiquitin; D017351:N-Acetylglucosaminyltransferases
keywords: Cross-talk; F-box protein; FBXO4; FBXW10; O-GlcNAcylation; Ubiquitination