PMID- 15543578 OWN - NLM STAT- MEDLINE DCOM- 20050809 LR - 20081121 IS - 0730-2312 (Print) IS - 0730-2312 (Linking) VI - 94 IP - 3 DP - 2005 Feb 15 TI - Histone acetyltransferase activity of p300 enhances the activation of IL-18 promoter. PG - 566-72 AB - Interleukin-18 (IL-18), an important regulator of innate and acquired immune responses expressed from a variety of cell types, is a pleiotropic cytokine in the development of T helper type 1 (Thl) cells. The p300/CBP (CREB-binding protein) coactivator proteins are important histone acetyltransferases (HATs) that regulate the transcription of many genes. Whether p300/CBP play a role in the IL-18 expression has not been investigated previously. In this study, we analyzed the roles of p300 in the regulation of mouse IL-18 by using RT-PCR and a series of co-transfection studies. We showed that p300 had a stimulating effect on the endogenous IL-18 mRNA synthesis and on the activity of IL-18 p1 promoter. The results also showed that IL-18 p1 promoter activity was enhanced by p300 in a dose-dependent manner. Moreover, the p300-mediated activation function can be suppressed by the adenovirus E1A protein, which inhibits the HAT function of p300. Also, a mutation in p300 HAT region abolished the effect of p300 on IL-18 activation. These data further indicate that the acetylase activity of p300 was indispensable to its function. Furthermore, we found that p300 was able to enhance the effect of the transcription factor c-Fos on activation of the IL-18 promoter. Data presented in this paper implicate important roles of p300 in the transcriptional regulation of IL-18. CI - Copyright 2004 Wiley-Liss, Inc. FAU - Sun, Haijing AU - Sun H AD - Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, P.R. China. FAU - Lu, Jun AU - Lu J FAU - Xu, Xin AU - Xu X FAU - Jin, Shunzi AU - Jin S FAU - Wang, Xiuli AU - Wang X FAU - Wei, Liang AU - Wei L FAU - Dong, Mei AU - Dong M FAU - Huang, Baiqu AU - Huang B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Cell Cycle Proteins) RN - 0 (DNA Primers) RN - 0 (Interleukin-18) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - EC 2.3.1.- (Acetyltransferases) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (p300-CBP Transcription Factors) RN - EC 2.3.1.48 (p300-CBP-associated factor) SB - IM MH - Acetyltransferases/*metabolism MH - Animals MH - Base Sequence MH - Cell Cycle Proteins/*metabolism MH - DNA Primers MH - Histone Acetyltransferases MH - Interleukin-18/*genetics MH - Mice MH - *Promoter Regions, Genetic MH - RNA, Messenger/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transcription Factors/*metabolism MH - Transcription, Genetic MH - p300-CBP Transcription Factors EDAT- 2004/11/16 09:00 MHDA- 2005/08/10 09:00 CRDT- 2004/11/16 09:00 PHST- 2004/11/16 09:00 [pubmed] PHST- 2005/08/10 09:00 [medline] PHST- 2004/11/16 09:00 [entrez] AID - 10.1002/jcb.20194 [doi] PST - ppublish SO - J Cell Biochem. 2005 Feb 15;94(3):566-72. doi: 10.1002/jcb.20194.