Vakhrusheva O, Braeuer D, Liu Z, Braun T, Bober E
Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
J Physiol Pharmacol. 2008 Dec;59 Suppl 9:201-12.
Mammalian sirtuins, Sirt1-Sirt7, are recently discovered regulatory proteins, which play decisive roles in cellular metabolism, stress resistance, and proliferation. Sirtuins are homologs of the founder member of the sirtuin family, the yeast Sir2. Sir2 encodes a NAD(+)-dependent histone deacetylase and its overexpression extends the lifespan through silencing of specific chromatin regions. Lifespan extension by Sir2 homologs was also demonstrated in more complex species such as C. elegans and D. melanogaster. A longevity function has been also postulated for mammalian sirtuins, however definitive proof is still lacking. Here, we have investigated the role of the mouse Sirt7 in the control of cellular growth and proliferation. Using Sirt7 knockout and overexpressing cells we demonstrate an anti-proliferative role of Sirt7. We also show that Sirt7 expression inversely correlates with the tumorigenic potential of several murine cell lines. Considering the known role of Sirt7 as an activator of rDNA transcription we propose that Sirt7 may enable cells to sustain critical metabolic functions by inhibiting cell growth even under severe stress conditions. We conclude, that these Sirt7 functions may improve tissue integrity in aged animals.
哺乳动物的沉默调节蛋白Sirt1 - Sirt7是最近发现的调节蛋白，它们在细胞代谢、应激抗性和增殖中起决定性作用。沉默调节蛋白是沉默调节蛋白家族创始成员酵母Sir2的同源物。Sir2编码一种依赖烟酰胺腺嘌呤二核苷酸（NAD(+)）的组蛋白脱乙酰酶，其过表达通过使特定染色质区域沉默来延长寿命。在更复杂的物种如秀丽隐杆线虫和黑腹果蝇中也证明了Sir2同源物可延长寿命。哺乳动物沉默调节蛋白也被推测具有长寿功能，然而仍缺乏确凿证据。在此，我们研究了小鼠Sirt7在控制细胞生长和增殖中的作用。使用Sirt7基因敲除和过表达细胞，我们证明了Sirt7具有抗增殖作用。我们还表明，Sirt7的表达与几种小鼠细胞系的致瘤潜力呈负相关。考虑到Sirt7作为核糖体DNA（rDNA）转录激活剂的已知作用，我们提出Sirt7可能通过即使在严重应激条件下也抑制细胞生长，使细胞能够维持关键的代谢功能。我们得出结论，这些Sirt7功能可能改善衰老动物的组织完整性。
