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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/4922| Title: | A238L Inhibits NF-ATc2, NF-B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C--Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300 |
| Authors: | Ministerio de Educación y Ciencia (España) Fundación Ramón Areces Centro de Investigación en Sanidad Animal (España) |
| Keywords: | PKC, protein kinase C |
| Publisher: | American Association of Immunologists |
| Description: | Article available at http://www.jimmunol.org/cgi/content/abstract/180/4/2429 The transcriptional coactivators CREB-binding protein and p300 regulate inducible transcription in multiple cellular processes and during the establishment of inflammatory and immune response. Several viruses have been shown to interfere with CREB-binding protein/p300 function, modulating their transcriptional activity. In this study, we report that the viral protein A238L interacts with the amino-terminal region of p300, inhibiting the acetylation and transcriptional activation of NF-ATc2, NF-B, and c-Jun in stimulated human T cells. We demonstrate that A238L modulates the autoacetylation of p300 without altering its intrinsic histone acetyl transferase activity. Furthermore, we show that the molecular mechanism of the inhibition executed by the viral protein is conducted through blocking protein kinase C (PKC)-p300 interaction and further acetylation in the amino-terminal transactivation domain of the coactivator, and that Ser384, within the CH1 domain, is essential for the full transcriptional activation of the coactivator. Moreover, we show that overexpression of an active form of PKC- reverts the A238L-mediated inhibition of the transcriptional activity of p300, showing, for the first time, a PKC--mediated up-regulation of the coactivator. These findings provide new strategies to develop therapies potentially useful in the control of disorders related to p300 deregulation This work was supported by grants from Ministerio de Educación y Ciencia (BFU2004-00298/BMC) and by an institutional grant from the Fundación Ramón Areces. A.G.G. was funded by Centro de Investigación en Sanidad Animal Peer reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/4922 |
| Other Identifiers: | The Journal of Immunology, 2008, 180: 2429-2442 0022-1767 (Print) 1550-6606 (Online) http://hdl.handle.net/10261/4922 |
| Appears in Collections: | Digital Csic |
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