Concerted activation of the Mdm2 promoter by p72 RNA helicase and the coactivators p300 and P/CAF.
A scarcely studied and under-recognized feature of RNA helicases is their ability to regulate gene transcription. In particular, very little is known about the role of p72 RNA helicase in gene regulation. Here, we have analyzed how this helicase may enhance promoter activity. We demonstrate that p72 RNA helicase forms complexes with the homologous coactivators p300 and CBP in vitro and in vivo, especially leading to an enhancement of the transactivation potential of their C-termini. In addition, we show that the p300/CBP-associated protein (P/CAF) also interacts with p72 RNA helicase, and both this interaction and the binding to p300/CBP are mediated by the N-terminal 63 amino acids of p72 RNA helicase. p300, P/CAF and p72 RNA helicase synergize to stimulate selected promoters, including the Mdm2 one. Notably, downregulation of p72 RNA helicase leads to reduced Mdm2 transcription. Furthermore, our data suggest that p72 RNA helicase activates the Mdm2 promoter in a p53 dependent and independent manner. Collectively, our results have unraveled a mechanism of how p72 RNA helicase can regulate gene transcription, namely by cooperating with p300/CBP and P/CAF. Thereby, p72 RNA helicase may not only be involved in the p53-Mdm2 regulatory loop, but also profoundly impact on the transcriptome through various CBP/p300 and P/CAF interacting proteins.
Shin
Sook
S
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Janknecht
Ralf
R
D000906:Antibodies; D000918:Antibody Specificity; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D017124:Conserved Sequence; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000737:chemistry / Q000378:metabolism*; D017930:Genes, Reporter; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000906:Antibodies; D018797:Cell Cycle Proteins; D053487:DEAD-box RNA Helicases; D050881:E1A-Associated p300 Protein; D051548:Histone Acetyltransferases; D008156:Luciferases; D020783:Matrix Metalloproteinase 7; D051736:Proto-Oncogene Proteins c-mdm2; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494360:EP300 protein, human; C497206:MDM2 protein, human; C060932:MMP7 protein, human; C102004:DDX17 protein, human