Anastasia Mylona

Birkbeck Career Development ISSF Fellow and Principal Investigator

a.mylona@mail.cryst.bbk.ac.uk

Based at Birkbeck

Personal Website

Mechanisms and biological function of multisite phosphorylation in signaling and disease

Protein phosphorylation is an important post-translational protein modification and a major regulatory mechanism of cellular signaling.  Deregulation of phosphorylation pathways commonly underlies disease aetiology. Proteins often get phosphorylated not only at one but at multiple sites by a single protein kinase. Multisite phosphorylation is a key regulatory mechanism in many cellular processes, and has been suggested to provide a precise tool to generate complex functional outputs from single kinase signaling inputs. Our research vision is to understand the mechanism and functional role of multisite phosphorylation in physiology and disease. In particular, we want to understand how multisite phosphorylation controls the activity of transcriptional regulators and subsequently the final biological response and how it can alter the architecture of signaling pathways in diseases like cancer, which may pave the way for novel treatments. For that purpose, we use a novel multidisciplinary methodology pipeline combining structural (time-resolved NMR, X-ray crystallography), biochemical and cell-based in vivo experimental strategies.

Selected publications

Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation
Mylona, A., Theillet, X-F., Foster, C., Cheng, T., Miralles, F., Selenko, P., Treisman, R.
Science (2016) 354 (6309):233-237
 
The E3 ubiquitin ligase TRIM7 mediates c-Jun/AP-1 activation by Ras signalling
Chakraborty, A., Diefenbacher, M.E., Mylona, A., Kassel, O., Behrens, A.
Nature Communications (2015) 6:6782
 
The essential function for serum response factor in T-cell development reflects its specific coupling to extracellular signal-regulated kinase signaling
Mylona, A., Nicolas, R., Maurice, D., Sargent, M., Tuil, D., Daegelen, D., Treisman, R., Costello, P.
Molecular and Cellular Biology (2011) 31 (2):267-276