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Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling

The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles incl...

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Autores principales: Cook, Simon J., Stuart, Kate, Gilley, Rebecca, Sale, Matthew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193418/
https://www.ncbi.nlm.nih.gov/pubmed/28548464
http://dx.doi.org/10.1111/febs.14122
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author Cook, Simon J.
Stuart, Kate
Gilley, Rebecca
Sale, Matthew J.
author_facet Cook, Simon J.
Stuart, Kate
Gilley, Rebecca
Sale, Matthew J.
author_sort Cook, Simon J.
collection PubMed
description The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles including the endoplasmic reticulum, endosomes, golgi and mitochondria to access specific substrates and influence cell physiology. In this article, we review two aspects of ERK1/2 signalling at the mitochondria that are involved in regulating cell fate decisions. First, we describe the prominent role of ERK1/2 in controlling the BCL2‐regulated, cell‐intrinsic apoptotic pathway. In most cases ERK1/2 signalling promotes cell survival by activating prosurvival BCL2 proteins (BCL2, BCL‐x(L) and MCL1) and repressing prodeath proteins (BAD, BIM, BMF and PUMA). This prosurvival signalling is co‐opted by oncogenes to confer cancer cell‐specific survival advantages and we describe how this information has been used to develop new drug combinations. However, ERK1/2 can also drive the expression of the prodeath protein NOXA to control ‘autophagy or apoptosis’ decisions during nutrient starvation. We also describe recent studies demonstrating a link between ERK1/2 signalling, DRP1 and the mitochondrial fission machinery and how this may influence metabolic reprogramming during tumorigenesis and stem cell reprogramming. With advances in subcellular proteomics it is likely that new roles for ERK1/2, and new substrates, remain to be discovered at the mitochondria and other organelles.
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spelling pubmed-61934182018-10-25 Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling Cook, Simon J. Stuart, Kate Gilley, Rebecca Sale, Matthew J. FEBS J State‐of‐the‐Art Review The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles including the endoplasmic reticulum, endosomes, golgi and mitochondria to access specific substrates and influence cell physiology. In this article, we review two aspects of ERK1/2 signalling at the mitochondria that are involved in regulating cell fate decisions. First, we describe the prominent role of ERK1/2 in controlling the BCL2‐regulated, cell‐intrinsic apoptotic pathway. In most cases ERK1/2 signalling promotes cell survival by activating prosurvival BCL2 proteins (BCL2, BCL‐x(L) and MCL1) and repressing prodeath proteins (BAD, BIM, BMF and PUMA). This prosurvival signalling is co‐opted by oncogenes to confer cancer cell‐specific survival advantages and we describe how this information has been used to develop new drug combinations. However, ERK1/2 can also drive the expression of the prodeath protein NOXA to control ‘autophagy or apoptosis’ decisions during nutrient starvation. We also describe recent studies demonstrating a link between ERK1/2 signalling, DRP1 and the mitochondrial fission machinery and how this may influence metabolic reprogramming during tumorigenesis and stem cell reprogramming. With advances in subcellular proteomics it is likely that new roles for ERK1/2, and new substrates, remain to be discovered at the mitochondria and other organelles. John Wiley and Sons Inc. 2017-06-18 2017-12 /pmc/articles/PMC6193418/ /pubmed/28548464 http://dx.doi.org/10.1111/febs.14122 Text en © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle State‐of‐the‐Art Review
Cook, Simon J.
Stuart, Kate
Gilley, Rebecca
Sale, Matthew J.
Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling
title Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling
title_full Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling
title_fullStr Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling
title_full_unstemmed Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling
title_short Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling
title_sort control of cell death and mitochondrial fission by erk1/2 map kinase signalling
topic State‐of‐the‐Art Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193418/
https://www.ncbi.nlm.nih.gov/pubmed/28548464
http://dx.doi.org/10.1111/febs.14122
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