MOLECULAR ONCOLOGY
p53–p21–DREAM/RB transcriptional repression

Research programme 01

p53–p21–DREAM/RB transcriptional repression

We define how p53 activation is relayed through p21 and pocket-protein complexes to silence hundreds of genes required for cell-cycle progression.

Central question

How do DREAM and RB cooperate to convert p53 activation into a complete and durable arrest programme?

p53 directly activates a relatively focused set of genes, but many of its most important arrest outputs arise through indirect repression. p21 inhibits cyclin-dependent kinases, allowing p130/p107 and RB to form DREAM and RB:E2F complexes at cell-cycle promoters.

p53–p21–RB signalling model. Figure 1 from Engeland, Cell Death & Differentiation (2022), “Cell cycle regulation: p53-p21-RB signaling.” Reused under CC BY 4.0.
p53–p21–RB signalling model. Figure 1 from Engeland, Cell Death & Differentiation (2022), “Cell cycle regulation: p53-p21-RB signaling.” Reused under CC BY 4.0.

Approaches

CRISPR knockout and isogenic cell systemsTranscriptome and promoter meta-analysisChromatin immunoprecipitation

Selected work

BRCA1 and BRCA2 gene expression: p53- and cell cycle-dependent repression requires RB and DREAM (2025)
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