1. CDK6 induces a transcriptional program to antagonize p53.
CDK6 induces a transcriptional program to antagonize p53. A, Heat maps of transcripts deregulated in Cdk6+/+, Cdk6K43M and Cdk6−/− colonies 10 days after BCR–ABL transduction (n = 4 colonies per genotype). B, Gene ontology (GO) analysis of genes regulated in a kinase-dependent manner in colonies 10 days after BCR–ABL transduction (upper table). Examples of deregulated genes involved in the p53 response (lower table). C, qPCR analysis of the p53 regulators Prmt5 and Mdm4 in individual colonies isolated from methylcellulose. **, P < 0.01; ***, P < 0.001; ****, P < D, Heat maps of transcripts deregulated in BCR–ABL+Cdk6+/+, Cdk6K43M and Cdk6−/− cell lines (n = 2 cell lines per genotype). E, Venn diagram showing the number of transcripts regulated in colonies and cell lines (blue circles) and the numbers of gene promoters with ChIP-seq peaks (red circle). The numbers in the intersecting areas show the overlap between the two datasets and the genes having a ChIP-seq peak in the promoter region. F, Representative examples of ChIP-seq peaks in the promoter regions of the p53 antagonists Prmt5 and Mdm4. G, Pie charts showing the functional classification of gene ontology terms identified in the gene sets that are bound by CDK6 and show expression changes in colonies or cell lines.
Florian Bellutti et al. Cancer Discov 2018;8:
©2018 by American Association for Cancer Research