Two tandem and independent sub-activation domains in the amino terminus of p53 require the adaptor complex for activity.
The ability of p53 to function as a tumor suppressor is linked to its function as a transcriptional activator, since p53 mutants that do not transactivate are unable to suppress tumor cell growth. Previous studies identified an activation domain in the amino terminal 40 residues of the protein, a region that binds to several general transcription factors and to some oncogene products. For example, mdm-2, a cellular oncoprotein, binds to this region and represses p53 transactivation. Here we describe a new activation domain within the amino terminus of p53 that maps between amino acids 40-83, and whose residues trp-53 and phe-54 are critical for function both in yeast and in mammalian cells. In vivo studies in yeast show that the new activation subdomain, unlike the previously described, is mdm-2 independent. Both p53 activation subdomains (1-40 and 40-83) require the yeast adaptor complex ADA2/ADA3/GCN5 for transcriptional activation. Moreover, since activation by p53 requires GCN5's enzymatic histone acetyltransferase domain, p53 may regulate gene expression by influencing chromatin modification.
Candau
R
R
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Scolnick
D M
DM
Darpino
P
P
Ying
C Y
CY
Halazonetis
T D
TD
Berger
S L
SL
D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics*; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D010449:Peptide Mapping; D011494:Protein Kinases / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011494:Protein Kinases; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C090575:ADA2 protein, S cerevisiae; C083323:NGG1 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor