SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation.
SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation.
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SIRT6 通过促进 p27Kip1 泛素蛋白酶体降解来延缓细胞衰老。
DOI：
10.18632/aging.101038
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发表时间：
2016-09-16
期刊：
影响因子：
--
通讯作者：
Tong T
中科院分区：
文献类型：
--
作者：
Zhao G;Wang H;Xu C;Wang P;Chen J;Wang P;Sun Z;Su Y;Wang Z;Han L;Tong T
Sirtuin 6（SIRT 6）是衰老和衰老相关疾病的关键因素。然而，SIRT 6在细胞衰老中的作用尚未完全了解。在这里，我们表明，SIRT 6抑制p27 Kip 1（p27）在细胞衰老的表达。SIRT 6的表达在细胞衰老过程中减少，而SIRT 6的表达增强促进细胞增殖并拮抗细胞衰老。此外，我们证明了SIRT 6促进蛋白酶体降解p27，SIRT 6降低了p27的乙酰化水平和蛋白半衰期。p27乙酰化增加了其蛋白质的稳定性。此外，SIRT 6直接与p27相互作用。重要的是，与那些年轻细胞相比，当细胞衰老时，p27被强烈乙酰化并且具有延长的蛋白质半衰期，SIRT 6减少。最后，SIRT 6显著地挽救了由p27诱导的衰老。我们的研究结果表明，SIRT 6降低p27乙酰化，导致其通过泛素-蛋白酶体途径降解，从而延缓细胞衰老。
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.
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DOI：
10.1042/cs20120190
发表时间：
2013-02
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Kitada M;Kume S;Takeda-Watanabe A;Kanasaki K;Koya D
通讯作者：
Koya D
影响因子：
14.9
作者：
Han L;Zhou R;Niu J;McNutt MA;Wang P;Tong T
通讯作者：
Tong T
影响因子：
13.8
作者：
Kugel, Site;Mostoslavsky, Raul
通讯作者：
Mostoslavsky, Raul
SIRT2 通过损害 Skp2 介导的 p27 降解抑制非小细胞肺癌细胞生长
影响因子：
--
作者：
Li Z;Huang J;Yuan H;Chen Z;Luo Q;Lu S
通讯作者：
Lu S
DOI：
10.1006/bbrc.2000.3000
发表时间：
2000-07-05
影响因子：
3.1
作者：
Frye, RA
通讯作者：
Frye, RA