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Histone Acetyltransferase Activity (histone + acetyltransferase_activity)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Analysis of genetic stability at the EP300 and CREBBP loci in a panel of cancer cell lines,

GENES, CHROMOSOMES AND CANCER, Issue 2 2003
Guy W. Tillinghast
EP300 (p300) and CREBBP (CBP) are highly related transcriptional co-activators possessing histone acetyltransferase activity. These proteins have been implicated in coordinating numerous transcriptional responses that are important in the processes of proliferation and differentiation. A role for EP300 and CREBBP as tumor suppressors in cancer has been suggested by the fact that they are targeted by viral oncogenes; there is an increased incidence of hematologic malignancies in mice monoallelic for CREBBP; and loss, albeit at a low frequency, of both EP300 alleles in epithelial cancers has been observed. Because the level of EP300/CREBBP appears to have a critical effect on integrating certain transcriptional processes, we sought to determine whether a loss in the combined gene dosage of EP300 and CREBBP might play a role in cancer. Accordingly, we screened a panel of 103 cell lines for loss of heterozygosity and found 35 and 51% LOH for the CREBBP and EP300 loci, respectively. Concordant loss of CREBBP and EP300 was not associated with mutations in important regions of the remaining EP300 or CREBBP genes. In addition, there did not appear to be a statistically significant selection in cancer cells, stratified by various criteria, for the concordant loss of EP300 and CREBBP. We conclude that EP300 and CREBBP rarely act as classical tumor suppressors in human cancer. Published 2003 Wiley-Liss, Inc. [source]

Role of plant CBP/p300-like genes in the regulation of flowering time

THE PLANT JOURNAL, Issue 1 2007
Soon-Ki Han
Summary CREB-binding protein (CBP) and its homolog p300 possess histone acetyltransferase activity and function as key transcriptional co-activators in the regulation of gene expression that controls differentiation and development in animals. However, the role of CBP/p300-like genes in plants has not yet been elucidated. Here, we show that Arabidopsis CBP/p300-like genes promote flowering by affecting the expression of a major floral repressor FLOWERING LOCUS C (FLC). Although animal CBP and p300 generally function as co-activators, Arabidopsis CBP/p300-like proteins are required for the negative regulation of FLC. This CBP/p300-mediated FLC repression may involve reversible protein acetylation independent of histone modification within FLC chromatin. [source]

Interleukin-4 activates androgen receptor through CBP/p300

THE PROSTATE, Issue 2 2009
Soo Ok Lee
Abstract BACKGROUND Aberrant activation of androgen receptor (AR) plays an important role in the progression of castration resistant prostate cancer. Interleukin-4 (IL-4) enhances AR activation in the absence of androgen and stimulates castration resistant growth of androgen-sensitive prostate cancer cells. However, the mechanism of IL-4 mediated AR activation has not yet been revealed. METHODS The effect of IL-4 on CBP/p300 expression was examined by Western blot analysis. The effect of IL-4 on the interactions of AR and CBP/p300 was examined by co-immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown CBP/p300 expression to examine the role of CBP/p300 expression on IL-4 mediated AR activation. RESULTS We found that IL-4 increases CBP/p300 protein expression and enhances interaction of AR with CBP/p300 proteins through an increase in the recruitment of CBP/p300 protein to the androgen responsive elements in the promoters of androgen responsive genes. Down regulation of CBP/p300 expression using CBP/p300 specific siRNA abolished IL-4 mediated AR activation, suggesting that CBP/p300 is responsible for AR activation induced by IL-4. Furthermore, AR activation can be enhanced by AR acetylation induced by IL-4 in prostate cancer cells. The IL-4 mediated AR acetylation can be blocked by knocking down CBP/p300 expression using CBP/p300 specific siRNA. CONCLUSION These results suggest that IL-4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity. Prostate 69: 126,132, 2009. © 2008 Wiley,Liss, Inc. [source]

Montelukast inhibits tumour necrosis factor-,-mediated interleukin-8 expression through inhibition of nuclear factor-,B p65-associated histone acetyltransferase activity

CLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2008
F. Tahan
Summary Background Montelukast is a potent cysteinyl leukotriene-1 receptor antagonist possessing some anti-inflammatory effects although the molecular mechanism of these anti-inflammatory effects is unknown. In this study, we aimed to investigate the effect of montelukast on nuclear factor (NF)-,B-associated histone acetylation activity in phorbol myristate acetate (PMA)-differentiated U937 cells. Methods We examined the inhibitory effects of montelukast on TNF-,-induced IL-8 production in PMA-differentiated U-937 cells. U-937 cells were exposed to PMA (50 ng/mL) for 48 h to allow differentiation to macrophages. Macrophages were then exposed to TNF-, (10 ng/mL) in the presence or absence of montelukast (0.01,10 ,m) for 24 h. After this time, the concentration of IL-8 in the culture supernatant was measured by sandwich-type ELISA kit. The effect of signalling pathways on TNF-,-induced IL-8 release was examined pharmacologically using selective NF-,B/IKK2 (AS602868, 3 ,m), (PD98059, 10 ,m) and p38 mitogen activated protein kinase (MAPK) (SB203580, 1 ,m) inhibitors. NF-,B DNA binding activity was measured by a DNA-binding ELISA-based assay. NF-,B-p65-associated histone acetyltransferase (HAT) activity was measured by immunoprecipitation linked to commercial flourescent HAT. Results TNF-,-induced IL-8 release was suppressed by an NF-,B inhibitor but not by MEK or p38 MAPK inhibitors. Montelukast induced a concentration-dependent inhibition of TNF-,-induced IL-8 release and mRNA expression that reached a plateau at 0.1 ,m without affecting cell viability. Montelukast did not affect NF-,B p65 activation as measured by DNA binding but suppressed NF-,B p65-associated HAT activity. Conclusion Montelukast inhibits TNF-,-stimulated IL-8 expression through changes in NF-,B p65-associated HAT activity. Drugs targeting these enzymes may enhance the anti-inflammatory actions of montelukast. [source]