P300/CBP

Cytokines such as TNFa and IL-1 3, acting via NF-kB, can induce histone acetylation in both a time- and concentration-dependent manner. Upon DNA binding, NF-kB recruits transcriptional coactivators such as CREB binding protein (CBP) and p300/CBP-associated factor (PCAF). 

Fig. 13.1 Stability regulation of p53 by early vs. late RNI actions. RNI by (in)directly activating ATR/ATM provoke phosphorylation ofp53. In turn tetramerization of p53 and binding of the coactivator p300/CBP will provoke gene activation. This may go along with RNI-evoked nuclear retention of ubiquitinated p53 although...

Fig. 13.3 HIF-la and p53 as mediators of RNI signaling. RNI affect HIF-la stabilization to promote its interaction with HIF-ip. Recruitment ofthe coactivator p300/CBP causes gene activation to elicit pathophysiological responses. RNI activate...

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... 

Structure of a HAT from the p300/CBP family has been long awaited, since these enzymes have no sequence similarity with enzymes of the GNAT and MYST families. The structure of the p300 HAT domain was solved very recently in complex with a Lys-GoA bi-substrate inhibitor, which required a highly intricate expression and purification protocol in order to produce a protein amenable to crystallization studies [24]. Analysis of the structure revealed however that, despite no sequence conservation, a similar structural core is observed as for the GNAT and MYST... 

Trievel, R.C., Li, F.Y. and Marmorstein, R. (2000) Application of a fluorescent histone acetyltransferase assay to probe the substrate specificity of the human p300/ CBP-associated factor. Analytical Biochemistry, 287, 319-328. 

---