P53 activated

Khan MZ, Brandimarti R, Patel JP, Huynh N, Wang J, Huang Z, Fatatis A, Meucci O (2004) Apoptotic and antiapoptotic effects of CXCR4 is it a matter of intrinsic efficacy Implications for HIV neuropathogenesis. AIDS Res Hum Retroviruses 20 1063-1071 Khan MZ, Shimizu S, Patel JP, Nelson A, Le MT, Mullen-Przeworski A, Brandimarti R, Fatatis A, Meucci O (2005) Regulation of neuronal P53 activity by CXCR4. Mol Cell Neurosci. (l) 58-66... 

Wallingford JB, Seufert DW, Virta VC, Vize PD 1997 p53 activity is essential for normal development in Xenopus. Curr Biol 7 747-757... 

SET7/9 modulates p53 activity in human cancer cells in vitro and in vivo [22] and also regulates NF-/vB-dependent inflammatory genes [31]. 

Protein recognition p53 activation cell cycle control... 

Evans, S. C., et ah. An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2. 

Wang, X., et al., p53 Activation by nitric oxide involves down-regulation of Mdm2./ Biol Chem, 2002, 277(18), 15697-702. 

USP7 human indirect p53 activation regulates p53 ubiquitination [36]... 

Bariev NA, Liu L, Chehab NH, Mansfield K, Harris KG, Halazonetis TD, Berger SL (2001) Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell 8 1243-1254... 

Ionov, Y, Nowak N, Perucho M, Markowitz S, Cowell JK (2004) Manipulation of nonsense mediated decay identifies gene mutations in colon cancer Cells with microsatellite instability. Oncogene 23 639-645 Ito A, Lai CH, Zhao X, Saito S, Hamilton MH, Appella E, Yao TP (2001) p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J 20 1331-1340... 

In contrast, Snyder has demonstrated that an RI derivative ofp53 can restore endogenous p53 activity the RI derivative induced apoptosis by activation of endogenous p53 and by restoration of function to several p53 DNA contact mutants. Rl-modified peptides have also been investigated as potential alternatives for bost defense peptides. Indeed, a RI derivative of indolicidin retained tbe antimicrobial and antiendotoxic acitivities of the natural peptide. As the antiendotoxin activities of the Rl-derivative were conserved these results might indicate the conservation of multiple immunomodulatory activities upon retro-inversion, highlighting the potential of this modification for therapeutic applications. 

ATM gene encodes a kinase essential for p53 activity. ATM is inactivated in ataxia telangiectasia, characterized by hypersensitivity to x-rays and predisposition to lymphomas. 

Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM (1999) A leucine-rich nuclear export signal in the p53 tetramerization domain regulation of subcellular localization and p53 activity by NES masking. EMBO J 18 1660-1672... 

Hie p53 protein stimulates transcription of various genes that carry the p53 DNA element in the promoter region. Table 14.1 shows some of the p53-activated genes. 

Table 14.1. Examples of p53-activated genes (according to Ko and Prives, 1996).

A detailed analysis of p53-activated genes has shown that this includes many genes that can generate or respond to oxidative stress (Polyak et al., 1997). The hnk between oxidative stress and p53 may be explained by the apoptotic effect of p53. It is plausible that formation of activated oxygen is involved in triggering of p53-mediated apoptosis. 

Normal p53 protein binds DNA in a sequence-specific manner and thus most likely regulates gene transcription. Co-transfection experiments show that wild-type p53 activates the expression of genes adjacent to a p53 DNA-bind-ing site. Cells bearing oncogenic forms of p53 have lost this activity. 

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