E2fs--a family of transcription factors responsible for helping turn genes 'on'--play central roles in controlling cell division, survival, and cancer. They can drive cell division and, if inappropriately activated, may trigger cell death, a protective mechanism against cancer development. Recent findings published in Nature co-led by TWRI's Dr. Rod Bremner turn two widely held notions--that E2fs are essential for division and can drive cell death--upside down.

Dr. Bremner speculates that, "Although cells can divide without E2fs they dislike doing so, perhaps because they don't have all the right equipment to copy their genetic information properly." Indeed, in the retina and other tissues, loss of E2f induced an increase in DNA damage.

Parallel studies with collaborator Dr. Gustavo Leone showed that activating E2fs are not required for cell division in multiple tissues in vivo, but that they are essential for cell survival. Dr. Bremner's lab focused on the developing retina and defined mechanisms to explain these phenomena. First, they showed that an unrelated protein family (Myc) promoted division in the absence of E2fs. Second, they discovered that E2fs promoted survival because they maintained levels of a protein called Sirt1. In cells without E2f, Sirt1 protein levels dropped and activated the p53 protein responsible for promoting cell death.

"Cancer cells often have high Myc levels, and combining that with low E2f could help these cells to divide and to induce mutations to escape natural and pharmaceutical attack. Understanding the effect of different combinations of Myc and E2f activity is important to define how best to treat different cancers."

Chen D, Pacal M, Wenzel P, Knoepfler PS, Leone G, Bremner R. Nature. 2009 Dec 17;462(7275):925-9. [Pubmed abstract]. Research supported by Canadian Institutes of Health Research.

Chong JL, Wenzel PL, Saenz-Robles MT, Nair V, Ferrey A, Hagan JP, Gomez YM, Sharma N, Chen HZ, Ouseph M, Wang SH, Trikha P, Culp B, Mezache L, Winton DJ, Sansom OJ, Chen D, Bremner R, Cantalupo PG, Robinson ML, Pipas JM, Leone G. Nature. 2009 Dec 17;462(7275):930-4. [Pubmed abstract]. Research supported by the National Institutes of Health.