title: SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation.
abstract: Sirtuin6(SIRT6) has been implicated as a key factor in aging and aging-related diseases. However, the role of SIRT6 in cellular senescence has not been fully understood. Here, we show that SIRT6 repressed the expression of p27Kip1(p27) in cellular senescence. The expression of SIRT6 was reduced during cellular senescence, whereas enforced SIRT6 expression promoted cell proliferation and antagonized cellular senescence. In addition, we demonstrated that SIRT6 promoted p27 degradation by proteasome and SIRT6 decreased the acetylation level and protein half-life of p27. p27 acetylation increased its protein stability. Furthermore, SIRT6 directly interacted with p27. Importantly, p27 was strongly acetylated and had a prolonged protein half-life with the reduction of SIRT6 when cells were senescent, compared with those young cells. Finally, SIRT6 markedly rescued senescence induced by p27. Our findings indicate that SIRT6 decreases p27 acetylation, leading to its degradation via ubiquitin-proteasome pathway and then delays cellular senescence.
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Ganye
authors: G
authors: Zhao
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Hui
authors: H
authors: Wang
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Chenzhong
authors: C
authors: Xu
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Pan
authors: P
authors: Wang
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Jun
authors: J
authors: Chen
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Pengfeng
authors: P
authors: Wang
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Zhaomeng
authors: Z
authors: Sun
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Yuanyuan
authors: Y
authors: Su
authors: MOE Key Laboratory of Protein Sciences, Department of Pharmacology, School of Medicine, Tsinghua University, Beijing, 100084, China.
authors: Zhao
authors: Z
authors: Wang
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Limin
authors: L
authors: Han
authors: Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modiﬁcations and Cell Function, Beijing, 100191, China.
authors: Tanjun
authors: T
authors: Tong
mesh_terms: D000107:Acetylation; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C436291:CDKN1B protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C516592:SIRT6 protein, human; D037761:Sirtuins
keywords: SIRT6; acetylation; cellular senescence; p27kip1; ubiquitination