A high-throughput loss-of-function screening identifies novel p53 regulators.
The p53 protein is a sequence-specific transcription factor that plays a crucial role in tumor suppression by inducing apoptosis or cell cycle arrest in response to cellular damage. To identify novel proteins involved in the regulation of p53 transcriptional activity we have performed a large scale RNA interference-based screen. We have identified four genes previously unknown to be involved in modulating p53 activity (GAS41, RPS6K4, RUNDC1 and CRMP-2). The interference of each of these four genes resulted in the upregulation of p53 transcriptional activity and, conversely, their overexpression resulted in the inhibition of p53 target promoters and p53-mediated apoptosis. These observations suggest a role for these genes as p53 inhibitors and imply that they may have oncogenic activity.
Llanos
Susana
S
Tumor Suppression Group, Spanish National Cancer Center (CNIO), Madrid, Spain.
Efeyan
Alejo
A
Monsech
Jorge
J
Dominguez
Orlando
O
Serrano
Manuel
M
D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C411296:TP53I3 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C109446:YEATS4 protein, human; C095114:collapsin response mediator protein-2; D008156:Luciferases; C115634:RPS6KA4 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa