Functional cross-talk between p73beta and NF-kappaB mediated by p300.
p73beta is associated with induction of apoptosis or cellular growth arrest, while NF-kappaB is closely related with promotion of resistance to programmed cell death. These biologically opposing activities between p73beta and NF-kappaB propose a regulatory mechanism of critical turning on/off in cellular apoptotic or survival responses. In this study, we demonstrate that NF-kappaB-mediated transactivation is specifically downregulated by p73beta; conversely, p73beta-transactivation is negatively regulated by functional expression of p65, NF-kappaB RelA subunit. The p73beta transactivation domain (TA) and p65 NH2-terminus are crucial for their negative regulation of p65- and p73beta-mediated transactivation, respectively. Furthermore, p65- or p73beta-interaction with p300 is reciprocally inhibited by their competitive binding to p300 in a restrict amount-dependent manner. Likewise, both p73beta-activated apoptosis and p65-dependent increase of cell viability are reciprocally repressed by p65 and p73beta, respectively. These results have important implications for p300-mediated regulatory mechanism between p73beta- and p65-transactivation, by which both p73beta and NF-kappaB could mutually affect on their biological activities. Therefore, we propose that p300 is a transactivational regulator of competitively balanced cross-talk between p73beta and p65.
Ryou
Sang-Mi
SM
Laboratory of Molecular Biology, Department of Biology, College of Natural Sciences, Chung-Ang University, Seoul, Republic of Korea.
Kang
Kyung-Hwa
KH
Jeong
Mi-Hee
MH
Kim
Jung-Woong
JW
An
Joo-Hee
JH
Lee
So-Youn
SY
Jang
Sangmin
S
Song
Peter I
PI
Choi
Kyung-Hee
KH
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse