Sirt7-dependent inhibition of cell growth and proliferation might be instrumental to mediate tissue integrity during aging.
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.
Vakhrusheva
O
O
Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
Braeuer
D
D
Liu
Z
Z
Braun
T
T
Bober
E
E
D000375:Aging; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D004275:DNA, Ribosomal / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004275:DNA, Ribosomal; C539736:Sirt7 protein, mouse; D037761:Sirtuins