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JNK signaling: Regulation and functions based on complex protein-protein partnerships

Zeke, A. and Misheva, M. and Reményi, Attila and Bogoyevitch, M. A. (2016) JNK signaling: Regulation and functions based on complex protein-protein partnerships. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 80 (3). pp. 793-835. ISSN 1092-2172

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Abstract

The c-Jun N-terminal kinases (JNKs), as members of the mitogenactivated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for -20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Item Type: Article
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
Q Science / természettudomány > QR Microbiology / mikrobiológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 27 Sep 2016 11:51
Last Modified: 27 Sep 2016 11:51
URI: http://real.mtak.hu/id/eprint/40186

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