title: Tudor staphylococcal nuclease (Tudor-SN), a novel regulator facilitating G1/S phase transition, acting as a co-activator of E2F-1 in cell cycle regulation.
abstract: Tudor staphylococcal nuclease (Tudor-SN) is a multifunctional protein implicated in a variety of cellular processes. In the present study, we identified Tudor-SN as a novel regulator in cell cycle. Tudor-SN was abundant in proliferating cells whereas barely expressed in terminally differentiated cells. Functional analysis indicated that ectopic overexpression of Tudor-SN promoted the G1/S transition, whereas knockdown of Tudor-SN caused G1 arrest. Moreover, the live-cell time-lapse experiment demonstrated that the cell cycle of MEF(-/-) (knock-out of Tudor-SN in mouse embryonic fibroblasts) was prolonged compared with wild-type MEF(+/+). We noticed that Tudor-SN was constantly expressed in every cell cycle phase, but was highly phosphorylated in the G1/S border. Further study revealed that Tudor-SN was a potential substrate of Cdk2/4/6, supportively, we found the physical interaction of endogenous Tudor-SN with Cdk4/6 in G1 and the G1/S border, and with Cdk2 in the G1/S border and S phase. In addition, roscovitine (Cdk1/2/5 inhibitor) or CINK4 (Cdk4/6 inhibitor) could inhibit the phosphorylation of Tudor-SN, whereas ectopic overexpression of Cdk2/4/6 increased the Tudor-SN phosphorylation. The underlying molecular mechanisms indicated that Tudor-SN could physically interact with E2F-1 in vivo, and could enhance the physical association of E2F-1 with GCN5 (a cofactor of E2F-1, which possesses histone acetyltransferase activity), and promote the binding ability of E2F-1 to the promoter region of its target genes CYCLIN A and E2F-1, and as a result, facilitate the gene transcriptional activation. Taken together, Tudor-SN is identified as a novel co-activator of E2F-1, which could facilitate E2F-1-mediated gene transcriptional activation of target genes, which play essential roles in G1/S transition.
authors: From the Departments of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Immunology, School of Basic Medical Sciences, Laboratory of Molecular Immunology, Research Center of Basic Medical Science, and the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Chao
authors: C
authors: Su
authors: From the Departments of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Immunology, School of Basic Medical Sciences, Laboratory of Molecular Immunology, Research Center of Basic Medical Science, and the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Chunyan
authors: C
authors: Zhang
authors: Immunology, School of Basic Medical Sciences, Laboratory of Molecular Immunology, Research Center of Basic Medical Science, and the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Adiam
authors: A
authors: Tecle
authors: From the Departments of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Immunology, School of Basic Medical Sciences, Laboratory of Molecular Immunology, Research Center of Basic Medical Science, and the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Xue
authors: X
authors: Fu
authors: the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Jinyan
authors: J
authors: He
authors: From the Departments of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Immunology, School of Basic Medical Sciences, Laboratory of Molecular Immunology, Research Center of Basic Medical Science, and the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Juan
authors: J
authors: Song
authors: From the Departments of Biochemistry and Molecular Biology, School of Basic Medical Sciences, the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Wei
authors: W
authors: Zhang
authors: From the Departments of Biochemistry and Molecular Biology, School of Basic Medical Sciences, the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Xiaoming
authors: X
authors: Sun
authors: From the Departments of Biochemistry and Molecular Biology, School of Basic Medical Sciences, the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Yuanyuan
authors: Y
authors: Ren
authors: the Institute of Medical Technology, University of Tampere, Tampere University Hospital, Biokatu 8, FI-33014 Tampere, Finland, and.
authors: Olli
authors: O
authors: Silvennoinen
authors: Immunology, School of Basic Medical Sciences, the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China.
authors: Zhi
authors: Z
authors: Yao
authors: the Department of Immunology, University of Manitoba, Winnipeg R3E 0T5, Canada.
authors: Xi
authors: X
authors: Yang
authors: the Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin 300070, China minxinw@126.com.
authors: Minxin
authors: M
authors: Wei
authors: From the Departments of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Immunology, School of Basic Medical Sciences, Laboratory of Molecular Immunology, Research Center of Basic Medical Science, and the Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 300070, China, the Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin, 300070, China, the Institute of Medical Technology, University of Tampere, Tampere University Hospital, Biokatu 8, FI-33014 Tampere, Finland, and yangj@tijmu.edu.cn.
authors: Jie
authors: J
authors: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D059447:Cell Cycle Checkpoints; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases; D016193:G1 Phase; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D015533:Transcriptional Activation
chemical_list: D016213:Cyclins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D009687:Nuclear Proteins; D018844:Cyclin-Dependent Kinases; D004720:Endonucleases; C095221:SND1 protein, human; C490640:Snd1 protein, mouse
keywords: Cell Cycle; Cyclin-dependent Kinase (CDK); E2F-1; G1/S Transition; Gene Transcription; Protein Phosphorylation; Transcription Coactivator; Transcription Regulation; Tudor-SN
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