A hallmark of p53 function is to regulate a transcriptional program in response to extracellular and intracellular stress that directs cell cycle arrest, apoptosis, and cellular senescence. Independent of the role of p53 in the nucleus, some of the anti-proliferative functions of p53 reside within the mitochondria . p53 can arrest cell growth in response to mitochondrial p53 in an EJ bladder carcinoma cell environment that is naïve of p53 function until induced to express p53 . TP53 can independently partition with endogenous nuclear and mitochondrial proteins consistent with the ability of p53 to enact senescence. In order to address the role of p53 in navigating cellular senescence through the mitochondria, we identified SirT3 to rescue EJ/p53 cells from induced p53-mediated growth arrest. Human SirT3 function appears coupled with p53 early during the initiation of p53 expression in the mitochondria by biochemical and cellular localization analysis. Our evidence suggests that SirT3 partially abrogates p53 activity to enact growth arrest and senescence. Additionally, we identified the chaperone protein BAG-2 in averting SirT3 targeting of p53 -mediated senescence. These studies identify a complex relationship between p53, SirT3, and chaperoning factor BAG-2 that may link the salvaging and quality assurance of the p53 protein for control of cellular fate independent of transcriptional activity.
by Jun Zhang, Jianhong Wang, Daoying Geng, Yuxin Li, Donglei Song, Yuxiang Gu
The 256-slice CT enables the entire brain to be scanned in a single examination. We evaluated the application of 256-slice whole-brain CT perfusion (CTP) in determining graft patency as well as ... mehr
by Ikuko Suzuki, Yoshiyuki Tsuboi, Masamichi Shinoda, Kazuo Shibuta, Kuniya Honda, Ayano Katagiri, Masaaki Kiyomoto, Barry J. Sessle, Shingo Matsuura, Kinuyo Ohara, Kentaro Urata, Koichi Iwata
To evaluate the involvement of the mitogen-activated protein kinase (MAPK) cascade in o ... mehr
by Frida Dangardt, Yun Chen, Krister Berggren, Walter Osika, Peter Friberg
We prospectively and longitudinally determined the effects of childhood obesity on arterial stiffening and vascular wall changes. Changes in arterial stiffness measured as pulse wave velocity (PWV) and ... mehr