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Author Zhan, Q.; Fan, S.; Bae, I.; Guillouf, C.; Liebermann, D.A.; O'Connor, P.M.; Fornace, A.J.J. file  url
Title Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis Type Journal Article
Year 1994 Publication Oncogene Abbreviated Journal Oncogene  
Volume 9 Issue 12 Pages 3743-3751  
Keywords Apoptosis/*genetics; Gene Expression Regulation/*drug effects/genetics/radiation effects; *Genes, p53; Humans; Mutagens/*toxicity; Neoplasms/genetics; Proto-Oncogene Proteins/*genetics; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; bcl-2-Associated X Protein  
Abstract DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53 and in some cases can cause apoptosis. M1 cells, which do not express the endogenous tumor suppressor gene p53, undergo apoptosis following activation of a temperature sensitive p53 transgene, where it has been shown that bax, an important mediator of apoptosis, is a p53 target gene (Selvakumaran et al, Oncogene 9, 1791-8, 1994). Since p53 can function as a transcription factor after activation by IR, the genetic response to this stress was examined in a panel of human cells with defined p53 status. Like the p53-regulated gene gadd45, bax was rapidly induced, as measured by increased mRNA levels, in the p53 wt (wild type) human myeloid line ML-1, and it was not induced in cells lacking functional p53. However, unlike other p53-regulated genes, bax was only induced in p53 wt cells in which IR also triggered apoptosis. In the case of bcl2, which opposes bax function, mRNA levels were reduced in ML-1 cells after IR. Thus, bax appears to be an unique p53-regulated gene in that its induction by IR not only requires functional p53 but also requires that the cells be apoptosis “proficient.”  
Call Number Serial 2172  
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Author Culmsee, C.; Mattson, M.P. file  url
Title p53 in neuronal apoptosis Type Journal Article
Year 2005 Publication Biochemical and Biophysical Research Communications Abbreviated Journal Biochem Biophys Res Commun  
Volume 331 Issue 3 Pages 761-777  
Keywords Animals; Apoptosis/*physiology; Apoptosis Regulatory Proteins; DNA Damage; Gene Expression Regulation; Humans; Neurodegenerative Diseases/*physiopathology; Neurons/*cytology/*physiology; Nuclear Proteins/physiology; Proto-Oncogene Proteins/physiology; Proto-Oncogene Proteins c-bcl-2/physiology; Proto-Oncogene Proteins c-mdm2; Synapses/physiology; Transcriptional Activation; Tumor Suppressor Protein p53/*physiology; bcl-2-Associated X Protein  
Abstract The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and activation of p53 can trigger apoptosis in many cell types including neurons. Apoptosis is a form of programmed cell death that occurs in neurons during development of the nervous system and may also be responsible for neuronal deaths that occur in neurological disorders such as stroke, and Alzheimer's and Parkinson's diseases. p53 production is rapidly increased in neurons in response to a range of insults including DNA damage, oxidative stress, metabolic compromise, and cellular calcium overload. Target genes induced by p53 in neurons include those encoding the pro-apoptotic proteins Bax and the BH3-only proteins PUMA and Noxa. In addition to such transcriptional control of the cell death machinery, p53 may more directly trigger apoptosis by acting at the level of mitochondria, a process that can occur in synapses (synaptic apoptosis). Preclinical data suggest that agents that inhibit p53 may be effective therapeutics for several neurodegenerative conditions.  
Call Number Serial 2167  
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