p53 Activation: a case against Sir.
The p53 tumor suppressor is a critical transcription factor for controlling cell growth and apoptosis during times of cellular stress. In this issue of Cancer Cell, Lain et al. have used a p53-responsive reporter gene as the readout for screening small-molecule activators of p53 that could potentially reduce tumor growth. Using this approach, tenovin-6 was identified as a potent SIRT1 and SIRT2 inhibitor that indirectly activated p53 at single-digit micromolar concentrations. The identification of a specific sirtuin inhibitor has broad implications in understanding sirtuin-p53 signaling and the development of novel chemotherapeutics.
Brooks
Christopher L
CL
Institute for Cancer Genetics, Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.
Gu
Wei
W
D002455:Cell Division; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D015398:Signal Transduction; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins