A novel cofactor for p300 that regulates the p53 response.
The ability of p53 to function as a transcription factor is instrumental in facilitating the response to cellular stress, and p300/CBP proteins, which act as coactivators for diverse transcription factors, participate in regulating p53 activity. We report a novel cofactor for p300 that facilitates the p53 response by augmenting p53-dependent transcription and apoptosis. JMY and p300 associate in physiological conditions, and, during the cellular stress response, the p300/JMY complex is recruited to activated p53. The bax gene is efficiently activated by JMY, and protein isoforms that arise through alternative splicing alter the functional outcome of the p53 response. The results provide compelling evidence that the p300/JMY coactivator complex plays a central role in facilitating the p53 response.
Shikama
N
N
Division of Biochemistry and Molecular Biology, University of Glasgow, United Kingdom.
Lee
C W
CW
France
S
S
Delavaine
L
L
Lyon
J
J
Krstic-Demonacos
M
M
La Thangue
N B
NB
D017209:Apoptosis; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D018797:Cell Cycle Proteins; C121977:JMY protein, human; C485677:Jmy protein, mouse; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein