Acetylation of p53 activates transcription dna
Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity.
Acetylation of p53 activates transcription through ... 
Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity.
Acetylation of p53 Activates Transcription through ...
As a DNA sequence-specific transcription factor, p53 exerts its functions by activating or repressing transcription of its target genes (Ko and Prives, 1996). p53 activates transcription of several genes, including p21/WAF1/CIP1, GADD45, and Mdm2 (Attardi et al., 2000), whose gene products are required to regulate cell cycle progression or the function of p53 itself Haupt et al. 1997, Kubbutat ...
Acetylation of p53 Activates Transcription through ...
Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity. Acetylation site substitutions reduced p53-dependent ...
p53 Acetylation: Regulation and Consequences
Importantly, while K120 acetylation is dispensable for p21 gene regulation, the formation of Tip60-p53 complexes at the p21 promoter and nearby histone H4 acetylation is required for p53-mediated induction of p21 expression (Figure 4) .Thus, Tip60 is an essential component of p53 signaling that activates p53 through direct association on target promoters as well as acetylation of p53 at K120.
The impact of acetylation and deacetylation on the p53 pathway
Acetylation of p53 is an important reversible enzymatic process that occurs in response to DNA damage and genotoxic stress and is indispensible for p53 transcriptional activity. p53 was the first non-histone protein shown to be acetylated by histone acetyl transferases, and a number of more recent in vivo models have underscored the importance of this type of modification for p53 activity.
Activation of p53 Sequence-Specific DNA Binding by ...
The tumor suppressor p53 exerts antiproliferation effects through its ability to function as a sequence-specific DNA-binding transcription factor. Here, we demonstrate that p53 can be modified by acetylation both in vivo and in vitro. Remarkably, the site of p53 that is acetylated by its coactivator, p300, resides in a C-terminal domain known to be critical for the regulation of p53 DNA binding.
Nuclear myosin 1 activates p21 gene transcription in ...
We show that upon DNA damage, NM1 forms a complex with p53 and activates the expression of checkpoint regulator p21 (Cdkn1A) by PCAF and Set1 recruitment to its promoter for histone H3 acetylation ...
Activation of p53 Sequence-Specific DNA Binding by ...
The acetylation by p300 of these lysines in the C terminus of p53 leads to a neutralization of positive charges that in turn could disrupt the tailâcore interaction and activate p53 DNA binding. To further confirm this hypothesis, we tested the effect of acetylation on the ability of the C-terminal peptide to activate p53 in trans .
Methylation-Acetylation Interplay Activates p53 in ...
The product of the TP53 gene (p53) is an important tumor suppressor mutated in more than half of all human cancers (19, 20).In addition, p53 regulates the response of cells to DNA-damaging agents, including those commonly used for cancer therapy (28, 32).In response to genotoxic stress, p53 exerts its function mostly as a sequence-specific transcription factor by activating expression of its ...
DNA damage activates p53 through a phosphorylation ...
This simplified model shows one way that p53 may be activated as a transcription factor in response to a DNA damage-inducing agent. p53 is modified at several additional sites, and these may function independently or in conjunction with acetylation to activate p53 in response to UV or other agents; modifications to other components also may be important.
DNA-dependent Acetylation of p53 by the Transcription ... 
Consensus site DNA-dependent acetylation of p53 using supercoiled plasmid DNA in vitro and in vivo. A, in vitro p53 acetylation. Human recombinant p53 (lanes 2â4) was purified from insect cells and incubated with p300 and supercoiled plasmid containing the p53-consensus site (pG13, lanes 4) or nonspecific DNA (pMG13, lanes 3).
Acetylation of the p53 DNA-Binding Domain Regulates ... 
The ability of p53 to induce apoptosis plays an important role in tumor suppression. Here, we describe a previously unknown posttranslational modification of the DNA-binding domain of p53. This modification, acetylation of lysine 120 (K120), occurs rapidly after DNA damage and is catalyzed by the MYST family acetyltransferases hMOF and TIP60.
Acetylation - Wikipedia 
Protein acetylation. Acetylation is an important modification of proteins in cell biology; and proteomics studies have identified thousands of acetylated mammalian proteins. Acetylation occurs as a co-translational and post-translational modification of proteins, for example, histones, p53, and tubulins.Among these proteins, chromatin proteins and metabolic enzymes are highly represented ...
Molecular Cell, Vol. 8, 1243â1254, December, 2001 ... 
Acetylation of p53 Activates Transcription through Recruitment of Coactivators/Histone Acetyltransferases kinase CAK (Ko et al., 1997), and the phosphoinositol 3 kinase family members ATM (Baninet al., 1998; Canman et al., 1998), ATR (Tibbetts et al., 1999), and DNA-PK (Lees-Milleretal.,1992;Shiehetal.,1997)phosphorylate
DNA damage activates p53 through a phosphorylation ... 
Abstract. Activation of p53-mediated transcription is a critical cellular response to DNA damage. p53 stability and site-specific DNA-binding activity and, therefore, transcriptional activity, are modulated by post-translational modifications including phosphorylation and acetylation.
The impact of acetylation and deacetylation on the p53 ... 
The p53 tumor suppressor is a sequence-specific transcription factor that undergoes an abundance of post-translational modifications for its regulation and activation. Acetylation of p53 is an important reversible enzymatic process that occurs in response to DNA damage and genotoxic stress and is indispensible for p53 transcriptional activity. p53 was the first non-histone protein shown to be ...
ZNF509S1 downregulates PUMA by inhibiting p53K382 ... 
We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter.
Acetylation of p53 augments its site-specific DNA binding ... 
p53 acetylation levels correlate well with p53-mediated transcrip-tional activation in vivo. Thus, our results clarify some of the confusion surrounding acetylation-mediated effects on p53 bind-ing to DNA and suggest that acetylation of p53 in vivo may contribute, at least in part, to its transcriptional activation functions. ChIP transcription ...
DNA damage activates p53 through a phosphorylation ... 
DNA damage activates p53 through a phosphorylationâacetylation cascade Kazuyasu Sakaguchi,1 Julio E. Herrera,2 Shinâichi Saito, 3Toru Miki, Michael Bustin,2 Alex Vassilev,4 Carl W. Anderson,5,6 and Ettore Appella1 1Laboratory of Cell Biology, 2Laboratory of Molecular Carcinogenesis, and 3Laboratory of Cellular and Molecular Biology, National Cancer Institute (NCI), 4Laboratory of Molecular ...
(PDF) Methylation-Acetylation Interplay Activates p53 in ... 
Methylation-Acetylation Interplay Activates p53 in Response to DNA Damage Article (PDF Available) in Molecular and Cellular Biology 27(19):6756-69 · November 2007 with 76 Reads How we measure 'reads'
Regulation of p53 in response to DNA damage | Oncogene 
Activation of p53 can occur in response to a number of cellular stresses, including DNA damage, hypoxia and nucleotide deprivation. Several forms of DNA damage have been shown to activate p53 ...
Methylation-Acetylation Interplay Activates p53 in ... 
Methylation-Acetylation Interplay Activates p53 in Response to DNA Damage Gleb S. Ivanov, 1 â Tatyana Ivanova, â Julia Kurash, â ⥠Alexey Ivanov, 2 Sergey Chuikov, 3
Specific Acetylation of p53 by HDAC Inhibition Prevents ... 
By overexpressing a collection of p53 acetylation mutants in neurons, we show that specific acetylation at lysine 382, and to a lesser extent at lysine 381, is sufficient for suppressing the transactivation of p53-dependent gene targets and promoting the survival of neuronal cultures exposed to DNA damage or death-inducing levels of p53 (Figs. 6AâC, 10).
Acetylation of p53 activates transcription through ... 
Sigma-Aldrich offers abstracts and full-text articles by [N A Barlev, L Liu, N H Chehab, K Mansfield, K G Harris, T D Halazonetis, S L Berger].
Tip60-mediated acetylation activates transcription ... 
Acetylation of pro-apoptotic molecules such as p53 and p73α activates selective transactivation function towards apoptotic genes, bax and puma through enhanced promoter DNA binding [11, 15]. On the other hand, acetylation of Sp1 is shown to loosen binding to bak promoter consequently allowing access of Sp3 to the promoter region to drive bak transcription [ 16 ].
ZNF509S1 downregulates PUMA by inhibiting p53K382 ... 
ZNF509S1 decreases apoptosis induced by severe DNA damage only in the presence of p53. âą ZNF509S1 represses PUMA gene transcription induced by etoposide.. ZNF509S1 inhibits binding of p53 to the PUMA promoter via direct interaction with p53.. ZNF509S1 modulates acetylation of p53 K382 by p300.
HIPK2 contributes to PCAF-mediated p53 acetylation and ... 
DNA damage is widely believed to activate p53 as transcription factor through post-translational modifications and the modulation of specific target genes mediates most of the p53 oncosuppressor ...
Temporal and Differential Regulation of KAISO-controlled ... 
Transient transcription assays of pG5-p53RE-Luc constructs with various p53REs revealed that p53 activates KAISO (ZBTB33) transcription by acting on p53RE1 (-4326 to -4227) of the 5'-upstream region and on p53RE3 (+2929 to +2959) of the exon 2 coding region during early DNA damage responses (DDRs).
DNA Damage-Dependent Acetylation of p73 Dictates the ... 
Even though p53 acetylation has convincingly been shown to increase its affinity for DNA targets, the functional consequences of such acetylation remain obscure. In fact, nonacetylatable p53 mutants retain an almost intact ability to activate transcription (Liu et al., 1999).
Acetylation Is Indispensable for p53 Activation: Cell 
The activation of the tumor suppressor p53 facilitates the cellular response to genotoxic stress; however, the p53 response can only be executed if its interaction with its inhibitor Mdm2 is abolished. There have been conflicting reports on the question of whether p53 posttranslational modifications, such as phosphorylation or acetylation, are essential or only play a subtle, fine-tuning role ...
Promoter-specific p53-dependent histone acetylation ... 
We have used chromatin immunoprecipitation (ChIP) to measure p53-dependent histone acetylation at the p21, MDM2, and PUMA promoters. The pattern of histone acetylation was different at each promoter.
DNA-dependent Acetylation of p53 by the Transcription ... 
The IHD and IBiD minidomains of p300 also functioned as dominant negative inhibitors of p53-dependent transcription in vivo. Upon examining the affects of p300 binding on substrate acetylation, we found that the p53 consensus site DNA promotes a striking increase in p53 acetylation in vitro.
RESEARCH Open Access Tip60-mediated acetylation activates ... 
Tip60-mediated acetylation activates transcription independent apoptotic activity of Abl Zhihua Jiang1, ... In the case of p53, acetylation is shown to sti-mulate DNA-binding, stability and pro-apoptotic activity * Correspondence: ... tion of Pol II largest subunit and for transcription enhancement function of Abl [28].
Methylation-Acetylation Interplay Activates p53 in ... 
These p53 modification events can be observed on the promoter of p21 gene, a known transcriptional target of p53. Finally, we show that methylation-acetylation interplay in p53 augments acetylation of histone H4 in the promoter of p21 gene, resulting in its subsequent transcriptional activation and, hence, cell cycle arrest.
Human EHMT2/G9a activates p53 through methylation ... 
Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell 2001; 8 : 1243â1254. CAS Article PubMed PubMed Central Google Scholar
Acetylation of the DNA Binding Domain Regulates ...
We and others identified acetylation of the p53 DNA binding domain at lysine 120 as a critical event in apoptosis induction. Although initial studies showed that Lys-120 acetylation plays a role in p53 function in the nucleus, we report here a role for Lys-120 acetylation in transcription-independent apoptosis.
Methylation-acetylation interplay activates p53 in ...
Sigma-Aldrich offers abstracts and full-text articles by [Gleb S Ivanov, Tatyana Ivanova, Julia Kurash, Alexey Ivanov, Sergey Chuikov, Farid Gizatullin, Enrique M Herrera-Medina, Frank Rauscher, Danny Reinberg, Nickolai A Barlev].
Acetylation of Mouse p53 at Lysine 317 Negatively ...
Acetylation of Mouse p53 at Lysine 317 Negatively Regulates p53 Apoptotic Activities after DNA Damageâ Connie Chao, 1 Zhiqun Wu, Sharlyn J. Mazur, 2 Helena Borges, 1 Matteo Rossi, Tongxiang Lin,
Crosstalk between sumoylation and acetylation regulates ...
Interestingly, acetylation of p53 by p300 restores the DNAâbinding activity of Suâp53, indicating that acetylation antagonizes sumoylationâmediated inhibition of p53 function and thereby accounts for a stimulating role of p300âmediated acetylation in p53âdependent chromatin transcription in vivo and in vitro .
Nuclear myosin 1 activates p21 gene transcription in ...
NM1 KO cells exhibit increased DNA damage and changes in cell cycle progression, proliferation, and apoptosis, compatible with a phenotype resulting from impaired p53 signaling. We show that upon DNA damage, NM1 forms a complex with p53 and activates the expression of checkpoint regulator p21 (Cdkn1A) by PCAF and Set1 recruitment to its promoter for histone H3 acetylation and methylation.
Acetylation of the DNA Binding Domain Regulates ...
As mentioned above, acetylation of Lys-120 within the p53 DNA binding domain is also specifically required for p53-induced apoptosis (14, 19). Mechanistically, Lys-120 acetylation is necessary for p53 to activate the transcription of a subset of pro-apoptotic target genes, such as PUMA and BAX.
Functional analysis of the acetylation of human p53 in DNA ...
Tumor suppressor p53 is a transcription factor that directly activates the transcription of hundreds of genes, including p21, Mdm-2, noxa, and puma that are mediating p53-dependent functions (Vousden and Prives, 2009).In addition, p53 also directly suppresses the expression of a number of genes, such as Nanog (Lin et al., 2005).While p53 remains in an unstable and inactive state in normal ...
Acetylation of the p53 DNA-binding domain regulates ...
The acetylation of lysine 120 within the DNA binding domain of p53 is distinct from most other sites of p53 modification in that it is disrupted by mutation in human cancer. Also unusual is that this naturally occurring p53 mutation selectively affects the ability of p53 to induce apoptosis without blocking cell cycle arrest.
ING1 Represses Transcription by Direct DNA Binding and ...
The ING family of proteins is involved in the regulation of diverse processes ranging from cell cycle and cellular senescence to apoptosis. These effects are most likely through activation of acetylation-dependent pathways that ultimately alter gene expression. Despite reports linking ING to p53 activation, the molecular basis of how ING activates p53 function has not been elucidated.
Regulation of the p53 transcriptional activity
be a transcription factor. To activate down-streamtargetgenes,ïŹrstofall,theremusthave sufïŹcient p53 being present in the nucleus. p53 DBD then must bind to the speciïŹc DNA sequence (p53 responsive element) usually located in the promoters of target genes. Finally, p53 AD must be able to recruit the basal transcriptional machinery, and co ...
Regulation of p53 in Response to DNA Damage
Activation of p53 can occur in response to a number of cellular stresses, including DNA damage, hypoxia and nucleotide deprivation. Several forms of DNA damage have been shown to activate p53, including those generated by ionising radiation (IR), radio-mimetic drugs, ultraviolet light (UV) and chemicals such as methyl methane sulfonate (MMS).
RNA content in the nucleolus alters p53 acetylation via ...
Acetylation of p53 is sufïŹcient to abrogate its ubiquitination by HDM2. There is a direct competition between acetylation and ubi-quitination of the same C-terminal lysine residues in p53 (Li et al, 2002). In addition, the acetylation of p53 enhances sequence-speciïŹc DNA binding of p53 (Gu and Roeder, 1997;
Activation of p53 Function by Human Transcriptional ...
DNA, activate p53 DNA binding, and, thereby, regulate p53 functions. In conclusion, PC4 activates p53 recruitment to p53-responsive promoters (Bax and p21) in vivo through its interaction with p53 ...