Functional analysis of the p300 acetyltransferase domain: the PHD finger of p300 but not of CBP is dispensable for enzymatic activity

Bordoli, Lorenza; Hüsser, Susanne; Lüthi, Urs; Netsch, M.; Osmani, Hatam; Eckner, Richard

doi:10.1093/nar/29.21.4462

Cited by 79 publications

(64 citation statements)

References 51 publications

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“…For example, there is a differential requirement for the PHD fingers (in the C/H2 region) of p300 and CBP in their acetyltransferase activities. While CBP requires an intact PHD finger motif to acetylate histones and p53, p300 does not (5,21). This suggests that structural differences between p300 and CBP may contribute to the specialized functions of the proteins.…”

Section: Discussionmentioning

confidence: 99%

p53 Targets Simian Virus 40 Large T Antigen for Acetylation by CBP

Poulin

Kung

DeCaprio

2004

J Virol

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Simian virus 40 (SV40) large T antigen (T Ag) interacts with the tumor suppressor p53 and the transcriptional coactivators CBP and p300. Binding of these cellular proteins in a ternary complex has been implicated in T Ag-mediated transformation. It has been suggested that the ability of CBP/p300 to modulate p53 function underlies p53's regulation of cell proliferation and tumorigenesis. In this study, we provide further evidence that CBP activity may be mediated through its synergistic action with p53. We demonstrate that SV40 T Ag is acetylated in vivo in a p53-dependent manner and T Ag acetylation is largely mediated by CBP. The acetylation of T Ag is dependent on its interaction with p53 and on p53's interaction with CBP. We have mapped the site of acetylation on T Ag to the C-terminal lysine residue 697. This acetylation site is conserved between the T antigens of the human polyomaviruses JC and BK, which are also known to interact with p53. We show that both JC and BK T antigens are also acetylated at corresponding sites in vivo. While other proteins are known to be acetylated by CBP/p300, none are known to depend on p53 for acetylation. T Ag acetylation may provide a regulatory mechanism for T Ag binding to a cellular factor or play a role in another aspect of T Ag function.

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Section: Discussionmentioning

confidence: 99%

p53 Targets Simian Virus 40 Large T Antigen for Acetylation by CBP

Poulin

Kung

DeCaprio

2004

J Virol

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“…The PHD finger domain is shared by various nuclear proteins and has been proposed to be involved in protein-protein interactions (Aasland et al, 1995). In animals, the PHD finger domain is known among transcriptional co-regulators and proteins in chromatin modifying complexes, such as Jade-1, p300, CBP and ING1 (Aasland et al, 1995;Bordoli et al, 2001;Feng et al, 2002;Panchenko et al, 2004) and constitutes a highly specialized trimethyl-lysine binding domain (Li et al, 2006;Peña et al, 2006;Shi et al, 2006;Wysocka et al, 2006). In plants, the PHD finger domain has been identified in MS1, MMD, EBS and VIN3, which are regarded as putative transcriptional regulators involved in fertility or flowering (Wilson et al, 2001;Pineiro et al, 2003;Yang et al, 2003;Sung and Amasino, 2004).…”

Section: Obe1 and Obe2 Encode Phd Finger Proteinsmentioning

confidence: 99%

TheArabidopsis OBERON1andOBERON2genes encode plant homeodomain finger proteins and are required for apical meristem maintenance

et al. 2008

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Maintenance of the stem cell population located at the apical meristems is essential for repetitive organ initiation during the development of higher plants. Here, we have characterized the roles of OBERON1 (OBE1) and its paralog OBERON2 (OBE2), which encode plant homeodomain finger proteins, in the maintenance and/or establishment of the meristems in Arabidopsis. Although the obe1 and obe2 single mutants were indistinguishable from wild-type plants, the obe1 obe2 double mutant displayed premature termination of the shoot meristem, suggesting that OBE1 and OBE2 function redundantly. Further analyses revealed that OBE1 and OBE2 allow the plant cells to acquire meristematic activity via the WUSCHEL-CLAVATA pathway, which is required for the maintenance of the stem cell population, and they function parallel to the SHOOT MERISTEMLESS gene, which is required for preventing cell differentiation in the shoot meristem. In addition, obe1 obe2 mutants failed to establish the root apical meristem, lacking both the initial cells and the quiescent center. In situ hybridization revealed that expression of PLETHORA and SCARECROW, which are required for stem cell specification and maintenance in the root meristem, was lost from obe1 obe2 mutant embryos. Taken together, these data suggest that the OBE1 and OBE2 genes are functionally redundant and crucial for the maintenance and/or establishment of both the shoot and root meristems.

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“…The HAT activity of p300 is required for the functions of diverse proteins in transcriptional activation (42,52,54). The PHD finger of p300 has been reported to be dispensable for its HAT activity and its transactivating function (7). p300 protein can also acetylate certain nonhistone transcription-related proteins, including transcriptional activators (20), coactivators (12), and basal transcription factors (28).…”

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confidence: 99%

Cardiac p300 Is Involved in Myocyte Growth with Decompensated Heart Failure

Yanazume

Hasegawa

Morimoto

et al. 2003

Molecular and Cellular Biology

219

190

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A variety of stresses on the heart initiate a number of subcellular signaling pathways, which finally reach the nuclei of cardiac myocytes and cause myocyte hypertrophy with heart failure. However, common nuclear pathways that lead to this state are unknown. A zinc finger protein, GATA-4, is one of the transcription factors that mediate changes in gene expression during myocardial-cell hypertrophy. p300 not only acts as a transcriptional coactivator of GATA-4, but also possesses an intrinsic histone acetyltransferase activity. In primary cardiac myocytes derived from neonatal rats, we show that stimulation with phenylephrine increased an acetylated form of GATA-4 and its DNA-binding activity, as well as expression of p300. A dominant-negative mutant of p300 suppressed phenylephrine-induced nuclear acetylation, activation of GATA-4-dependent endothelin-1 promoters, and hypertrophic responses, such as increase in cell size and sarcomere organization. In sharp contrast to the activation of cardiac MEK-1, which phosphorylates GATA-4 and causes compensated hypertrophy in vivo, p300-mediated acetylation of mouse cardiac nuclear proteins, including GATA-4, results in marked eccentric dilatation and systolic dysfunction. These findings suggest that p300-mediated nuclear acetylation plays a critical role in the development of myocyte hypertrophy and represents a pathway that leads to decompensated heart failure.Heart failure arises from a number of diverse primary cardiovascular disorders and is associated with significant morbidity and mortality. Therefore, elucidating the mechanisms of this disease is of clinical importance. Previous studies have demonstrated that a variety of stresses on the heart activate neuronal and hormonal factors, such as the renin-angiotensin system and factors regulating the sympathetic nervous systems. These factors initiate a number of subcellular signaling pathways, which finally reach the nuclei of cardiac myocytes and change the pattern of gene expression associated with hypertrophy (reviewed in references 14 and 53). In order to establish appropriate therapy for heart failure, it is critical to identify a common nuclear pathway which can be targeted by pharmacological agents in the future.We have been interested in transcription factors that mediate changes in gene expression during myocardial-cell hypertrophy. A zinc finger protein, GATA-4, is one such factor and is required for transcriptional activation of cardiac genes whose expression is upregulated during myocardial-cell hypertrophy (22, 25; reviewed in reference 46). While overexpression of GATA-4 in cardiac myocytes causes hypertrophy, expression of a dominant-negative form of GATA-4 inhibits Gq protein-coupled receptor agonist-induced hypertrophy (37). During myocardial-cell hypertrophy, GATA-4 is phosphorylated at a serine residue and shows increased DNA-binding ability (38,47). Phosphorylation of cardiac GATA-4 requires activation of MEK1/extracellular signal-regulated kinase (ERK) 1/2. On the other hand, activation of MEK1 in...

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Functional analysis of the p300 acetyltransferase domain: the PHD finger of p300 but not of CBP is dispensable for enzymatic activity

Cited by 79 publications

References 51 publications

p53 Targets Simian Virus 40 Large T Antigen for Acetylation by CBP

p53 Targets Simian Virus 40 Large T Antigen for Acetylation by CBP

TheArabidopsis OBERON1andOBERON2genes encode plant homeodomain finger proteins and are required for apical meristem maintenance

Cardiac p300 Is Involved in Myocyte Growth with Decompensated Heart Failure

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