2016
DOI: 10.18632/aging.101038 View full text |Buy / Rent full text
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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 d… Show more

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“…p27 is a regulator of cyclin-dependent kinases (CDK); when bound, p27 inactivates CDKs and induces cell cycle arrest at G1, S, or G2 phases. 33 Our data demonstrated that siRNA knockdown of p27 rescued GBM cells from matrine-induced senescence and implicate p27 as a critical molecule mediating matrine-induced cellular senescence. Thus, we were able to demonstrate that matrine inhibits GBM cell growth through several components along the same pathway, which is illustrated in Figure 7.…”
Section: Discussionsupporting
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rupbmjkragerfmgwileyiopcupepmcmbcthiemesagefrontiersapsiucrarxivemeralduhksmucshluniversity-of-gavle
“…p27 is a regulator of cyclin-dependent kinases (CDK); when bound, p27 inactivates CDKs and induces cell cycle arrest at G1, S, or G2 phases. 33 Our data demonstrated that siRNA knockdown of p27 rescued GBM cells from matrine-induced senescence and implicate p27 as a critical molecule mediating matrine-induced cellular senescence. Thus, we were able to demonstrate that matrine inhibits GBM cell growth through several components along the same pathway, which is illustrated in Figure 7.…”
Section: Discussionsupporting
“…On protein blots, we only observed significant changes in p27 in response to matrine. p27 is a regulator of cyclin‐dependent kinases (CDK); when bound, p27 inactivates CDKs and induces cell cycle arrest at G1, S, or G2 phases . Our data demonstrated that siRNA knockdown of p27 rescued GBM cells from matrine‐induced senescence and implicate p27 as a critical molecule mediating matrine‐induced cellular senescence.…”
Section: Discussionmentioning
“…The sirtuins are members of a family of deacetylases (SIRT1 through SIRT7) that modulate numerous cellular processes [ 53 ]. SIRT1 and SIRT6 are nucleus-localized sirtuins that also modulate cellular senescence, and downregulation of SIRT1 and SIRT6 has been demonstrated to induce premature senescence in a variety of cell types [ 81 , 82 , 83 ]. In the present study, we determined that BLU9931 reduced SIRT1 and SIRT6 levels, leading to the induction of premature senescence in PDAC cells ( Figure 6 ).…”
Section: Discussionmentioning
“…It was recently reported that sirtuin 6 (SIRT6), a protein presenting with HDAC-like senotherapeutic properties, inhibits NF-κB and EC senescence, suggesting AD therapeutic benefits (Lappas, 2012; Zhao et al, 2016).…”
Section: Senotherapeutics: Targeting Senescence In Alzheimer's Diseasementioning