E2F1
E2F1 is a transcription factor that activates the genes a cell needs to replicate its DNA.
Function
E2F1 drives transcription of genes for DNA synthesis: dihydrofolate reductase, thymidine kinase, cyclin E, and APAF1 among them. Its activity is gated by RB, which binds E2F1 at promoters and keeps them silent until cyclin-CDK phosphorylation releases it at the G1/S transition. E2F1 also induces p14ARF, which stabilizes p53 and triggers arrest or death when a cell is pushed into cycle without growth signals. E2F1 induces its own promoter as well, creating positive feedback that makes the entry into S phase switch-like.
In cancer
Because E2F1 activity is held down by RB, every tumor that disables RB - by mutation, by HPV E7, or by cyclin amplification - activates E2F1, and S-phase genes are transcribed on demand. The ARF loop is the reason unsolicited E2F1 activity is dangerous for the tumor: a proliferating cell must also lose p53 or ARF, or the E2F1 pulse kills it. Viral oncogenes target both gates together, which is how HPV converts infection to cancer.
Notes
- Human gene symbol: E2F1; UniProt Q01094; 437 amino acids; E2F/DP family, heterodimerizes with DP1.