Virology Faculty Member - Nicholas Dyson

Nicholas Dyson

Professor of Medicine
Laboratory of Molecular Oncology

Massachusetts General Hospital/East
Cancer Center, CNY Bldg.149, Rm. 7410
149 13th Street
Charlestown, MA 02129
Tel: 617-724-9888
Fax: 617-726-7808

I'm fascinated by the functions of the retinoblastoma tumor suppressor (RB). RB is a member of a group of related proteins, the pocket proteins, that control cell proliferation. During G1 to S phase of the cell cycle, activation of cyclin dependent kinases in G1 leads to the phosphorylation of pocket proteins, and a series of waves of E2F-dependent transcription. E2F co-ordinates the expression of a set of genes that encode proteins that are essential for DNA synthesis, and activation of E2F primes the cell for proliferation. E2F activation is normally a tightly controlled process but it is deregulated in most, if not all, tumor cells. Viral oncoproteins such as Adenovirus E1A, SV40 large T antigen and E7 proteins of human papillomaviruses have evolved to target RB and the viruses exploit these interactions to drive quiescent cells into the cell cycle.

The overall goal of my research is to understand how pRB and E2F act, what their targets are, how their functions are controlled, and the changes that occur when these proteins are mutated or deregulated. We use a combination of genetic and biochemical approaches, and work in two complementary model organisms. We have taken advantage of the streamlined nature of RB and E2F families in Drosophila to dissect the roles of E2F activator and repressor complexes. Studies in flies allow us to examine the roles of E2F and RBF in the context of animal development, and to screen for mutants that genetically interact with the RBF/E2F pathway.

In parallel we use mouse cells to dissect the functions of pRB. Current work involves the use of a knock-in allele that eliminates the highly conserved LXCXE-binding cleft on pRB. The LXCXE-binding cleft of pRB is not only required for pRB to be inactivated by viral oncoproteins, but it is also the binding site for multiple chromatin remodeling complexes, that are recruited by pRB in order to repress transcription. We are using this allele to figure out precisely which repressors are recruited by pRB to its specific targets, and to determine which types of cell cycle arrest depend on this particular surface of pRB.

Last Update: 10/22/2013


For a complete listing of publications click here.



Dick FA, Dyson N.. pRB Contains an E2F1 specific binding domain that allows E2F1 induced apoptosis to be regulated separately from other E2F activities.
Molecular Cell, 2003. 12(3): 639-49.

Dimova D, Stevaux O, Frolov MV, Dyson N.. Cell cycle dependent and cell cycle independent control of transcription by the Drosophila E2F/RB pathway. Genes and Development 2003, 17(18): 2308-20.

Korenjak M, Taylor-Harding B, Binné UK, Satterlee JS, Steveaux O, Aasland R, White-Cooper H, Dyson N, Brehm A.. Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes. Cell, 2004, 119(2): 181-

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