Mutations in the retinoblastoma gene lead to the development of tumours within the eye retina in young children. Approximately one child in every 15,000 to 30,000 births in the USA will develop a retinoblastoma. Most of these individuals are born with one mutant copy of the Retinoblastoma (Rb) gene, and develop the tumours when they acquire a second mutated copy. Rb plays an important role in controlling cell proliferation within the eye retina, and other cells, but how the action of Rb is controlled is not understood. New work to be published in the July issue of Nature Cell Biology (Vol. 3, No. 7, pp. 667-674) by Dr Nicholas La Thangue (University of Glasgow), and colleagues, has identified a new level of control of Rb function.
Modification is an important way to regulate the action of specific proteins and acetylation is a common mechanism by which proteins are modified. Rb is already modified through phosphorylation by cell cycle regulated proteins. La Thangue and colleagues show that Rb is also acetylated in a cell cycle regulated manner to control the action of the protein.
Infection of cells with adenovirus stimulates Rb acetylation. This acetylation prevents Rb undergoing phosphorylation.
Rb is acetylated in a complex by p300/CBP (proteins which contain histone acetyltransferase activity). p300/CBP are co-activators which are also important in controlling cell proliferation.
The adenovirus protein E1A binds p300 and recruits Rb into a complex which allows acetylation. Interestingly acetylated Rb interacts more strongly to a known oncogene, MDM2.
These results indicate that acetylation is an important way to control the activity of Rb. As a viral protein causes Rb to move into a complex which allows this acetylation to take place, this is probably a novel way to determine what function Rb has within the cell. By switching Rb modification between acetylation and phosphorylation the interaction of Rb with other oncogenes and proteins important in the regulation of cell proliferation can be tightly controlled.
Nicholas La Thangue
Tel: +44 141 330 5514
(C) Nature Cell Biology press release.
Message posted by: Trevor M. D'Souza