Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling.
Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling.
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通过ERK1/2 MAP激酶信号传导控制细胞死亡和线粒体裂变。
DOI：
10.1111/febs.14122
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Sale MJ
中科院分区：
文献类型：
--
作者：
Cook SJ;Stuart K;Gilley R;Sale MJ
ERK1/2信号通路最为人所知的是它在连接激活的生长因子受体和由于激活的ERK1/2进入细胞核并使转录因子磷酸化而引起的基因表达变化方面的作用。然而，激活的ERK1/2也转移到其他各种细胞器，包括内质网、内小体、高尔基体和线粒体，以获得特定的底物并影响细胞生理。在这篇文章中，我们回顾了线粒体ERK1/2信号的两个方面，这两个方面涉及到调节细胞命运的决定。首先，我们描述了ERK1/2在控制bcl2调控的细胞内固有的凋亡途径中的重要作用。在大多数情况下，ERK1/2信号通过激活促存活的bcl2蛋白(bcl2、bclxl和mcl1)和抑制促死亡蛋白(BAD、BIM、BMF和PUMA)来促进细胞存活。这种生存信号被癌基因增选来赋予癌细胞特异性的生存优势，我们描述了这种信息如何被用来开发新的药物组合。然而，ERK1/2也可以驱动促死亡蛋白noxA的表达，以控制营养饥饿期间的自噬或凋亡决定。我们还描述了最近的研究，证明了ERK1/2信号、Drp1和线粒体分裂机制之间的联系，以及这可能如何影响肿瘤发生和干细胞重新编程过程中的代谢重新编程。随着亚细胞蛋白质组学的进展，ERK1/2的新作用和新的底物很可能在线粒体和其他细胞器中仍有待发现。
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‐xL 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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影响因子：
16
作者：
Dehan, Elinor;Bassermann, Florian;Guardavaccaro, Daniele;Vasiliver-Shamis, Gaia;Cohen, Michael;Lowes, Kym N.;Dustin, Michael;Huang, David C. S.;Taunton, Jack;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Christoforou A;Mulvey CM;Breckels LM;Geladaki A;Hurrell T;Hayward PC;Naake T;Gatto L;Viner R;Martinez Arias A;Lilley KS
通讯作者：
Lilley KS
DOI：
10.1073/pnas.0703976104
发表时间：
2007-07-10
影响因子：
11.1
作者：
Brooks, Craig;Wei, Qingqing;Dong, Zheng
通讯作者：
Dong, Zheng