Negative feedback regulation of the ERK1/2 MAPK pathway

The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance

Establishing Priorities for the International Confederation of Plastic Surgery Societies

Background: The mission of the International Confederation of Plastic Surgery Societies (ICOPLAST) is to improve patient outcomes through collaboratively structured processes in education, advocacy and communication. This article explains how we approached the task of establishing priorities for this nascent confederation in an equitable and achievable manner. Methods: In late 2016, an online survey was sent to the inaugural 62 ICOPLAST member national societies for dissemination to their respective plastic surgeon members. Functional domains and proposed initiatives were ranked according to their level of importance by individual plastic surgeons. Results: The survey was completed by 572 plastic surgeons. As a functional domain, education was highly ranked by 75.3% of respondents, followed by patient safety (67.4%), communication (59.3%), humanitarian (46.6%), regulation (41.2%), and advocacy (41.1%). Respondents also ranked individual initiatives within each domain to produce a compilation list of the top 13 initiatives of importance. Conclusion: This study has identified priorities of importance to ICOPLAST members, which will aid in building a strategic framework and enhancing outcomes for patients, plastic surgeons, and the field of plastic surgery more broadly