Highlight Publication July 2007

Ewings KE, Hadfield-Moorhouse K, Wiggins CM, Wickenden JA, Balmanno K, Gilley R, Degenhardt K, White E, Cook SJ (2007)
ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL.
EMBO Journal 26 2856-2867
http://dx.doi.org/10.1038/sj.emboj.7601723

Lay Description

Apoptosis is the name used to describe a highly specialised form of cell death. This process is a normal part of embryo development, where it is responsible for the removal of unwanted cells. Defects in this process can give rise to developmental abnormalities; for example, failure to remove unwanted cells in the developing hand can lead to babies being born with webbed fingers. Apoptosis is also responsible for the removal of cells with mutations which could otherwise go on to cause diseases such as cancer or auto-immunity. Indeed, defects in apoptosis can contribute towards the development of cancer. Apoptosis is controlled by interactions between members of the BCL-2 family of proteins. Pro-survival BCL-2 proteins keep cells alive but they can be inactivated when pro-death proteins such as BIM bind to them.

In this study we were able to demonstrate that the interaction between BIM and the pro-survival proteins is regulated by survival signals within the cell. Specifically, we found that an enzyme called ERK, which promotes cell survival, was able to modify the BIM protein so that it could not interact with the pro-survival BCL-2 proteins. This has the effect of destabilizing the BIM protein so that is gets destroyed within the cell. Interestingly, many tumour cells exhibit a strong increase in ERK activity and this correlates with a decrease in BIM expression. Consequently this mechanism may contribute towards tumour cell survival.

About the Lead Author

Katherine Ewings comes from Brownhills in the West Midlands and gained a 1st in Biochemistry from the University of Leeds. After a year working at Dartmouth Medical School in the USA she joined Simon Cook’s lab at Babraham to do her PhD. She studied the regulation of the pro-apoptotic protein BIM by the pro-survival ERK1/2 signalling pathway. Katherine was awarded the Sir Michael Berridge Prize for 2005 for an outstanding piece of science at Babraham. She completed her PhD in 2005 and spent an extra year working at Babraham to complete the work for this paper. She is currently a post-doctoral research fellow at the Beatson Institute for Cancer Research in Glasgow.