A cryptic tubulin-binding domain links MEKK1 to curved tubulin protomers

Filipčík, Pavel; Latham, Sharissa L.; Cadell, Antonia L; Day, Catherine L.; Croucher, David R.; Mace, Peter D.

doi:10.1073/pnas.2006429117

Cited by 13 publications

(3 citation statements)

References 96 publications

(129 reference statements)

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“…MEKK1 protein is a key kinase activator for cell stress response. Activation of MEKK1 can stimulate a variety of reactions, including mitogen-activated protein (MAP) kinase and cell migration ( Filipcik et al., 2020 ). MEKK2 and MEKK3 belong to the MEKK/STE11 subfamily that is widely expressed and effective activators of the NF-κB and MAPK pathways ( Zhang et al., 2006 ).…”

Section: Resultsmentioning

confidence: 99%

Transcription level differences in Taxus wallichiana var. mairei elicited by Ce3+, Ce4+ and methyl jasmonate

Han

Geng²,

Li³

et al. 2022

Front. Plant Sci.

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Taxol is a precious and effective anticancer drug. Cerium and methyl jasmonate (MJ) have been shown to increase the yield of taxol in taxus cells. However, the mechanisms of cerium-mediated and MJ-mediated taxol biosynthesis remain unknown. RNA-Seq was applied to study the overall regulation mechanism of cerium and MJ on taxol biosynthesis and analyze the differences among T. mairei cells elicited by Ce3+, Ce4+ and MJ on transcriptional level . Using sequence homology, 179 unigenes were identified as taxol synthesis genes. Under the condition of 100 μM MJ, taxol synthesis genes were up-regulated. Notably, taxol synthesis genes were down-regulated expression at 1 mM Ce3+ and 1 mM Ce4+. Differential expression genes involved in some related functions were analyzed, such as MAPK signaling pathway and plant-pathogen interaction. Sequence alignment and phylogenetic analysis of nine differentially expressed WRKYs in our data were carried out.

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Section: Resultsmentioning

confidence: 99%

Transcription level differences in Taxus wallichiana var. mairei elicited by Ce3+, Ce4+ and methyl jasmonate

Han

Geng²,

Li³

et al. 2022

Front. Plant Sci.

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“…The observed differences in inhibition of the promoter activity by the MTAs might be explained by the different potentials to depolymerize the microtubule skeleton. Over the course of this study, Filipčík et al [ 37 ] have shown that the JNK upstream kinase MAPK kinase kinase 1 (MAP3K1) contains a tubulin-binding domain that interacts with soluble tubulin heterodimers leading to kinase activation. Hence, the strong increase in JNK activity is directly linked to the depolymerization of the tubulin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

The Microtubule-Targeting Agent Pretubulysin Impairs the Inflammatory Response in Endothelial Cells by a JNK-Dependent Deregulation of the Histone Acetyltransferase Brd4

Primke,

Ingelfinger,

Elewa

et al. 2023

Cells

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The anti-inflammatory effects of depolymerizing microtubule-targeting agents on leukocytes are known for a long time, but the potential involvement of the vascular endothelium and the underlying mechanistic basis is still largely unclear. Using the recently synthesized depolymerizing microtubule-targeting agent pretubulysin, we investigated the anti-inflammatory potential of pretubulysin and other microtubule-targeting agents with respect to the TNF-induced leukocyte adhesion cascade in endothelial cells, to improve our understanding of the underlying biomolecular background. We found that treatment with pretubulysin reduces inflammation in vivo and in vitro via inhibition of the TNF-induced adhesion of leukocytes to the vascular endothelium by down-regulation of the pro-inflammatory cell adhesion molecules ICAM-1 and VCAM-1 in a JNK-dependent manner. The underlying mechanism includes JNK-induced deregulation and degradation of the histone acetyltransferase Bromodomain-containing protein 4. This study shows that depolymerizing microtubule-targeting agents, in addition to their established effects on leukocytes, also significantly decrease the inflammatory activation of vascular endothelial cells. These effects are not based on altered pro-inflammatory signaling cascades, but require deregulation of the capability of cells to enter constructive transcription for some genes, setting a baseline for further research on the prominent anti-inflammatory effects of depolymerizing microtubule-targeting agents.

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“…Recently, a TOG domain has been identified in the region overlapping with the ARM that mediates interactions with AXIN1 [ 20 , 21 ]. The TOG domain preferentially binds with curved tubulin heterodimers, notwithstanding the biological functions of the MAP3K1–tubulin interactions are unclear [ 17 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Control of MAP3K1 in Eye Development and Sex Differentiation

Wang

Kimura

Mongan

et al. 2021

Cells

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The MAP3K1 is responsible for transmitting signals to activate specific MAP2K-MAPK cascades. Following the initial biochemical characterization, genetic mouse models have taken center stage to elucidate how MAP3K1 regulates biological functions. To that end, mice were generated with the ablation of the entire Map3k1 gene, the kinase domain coding sequences, or ubiquitin ligase domain mutations. Analyses of the mutants identify diverse roles that MAP3K1 plays in embryonic survival, maturation of T/B cells, and development of sensory organs, including eye and ear. Specifically in eye development, Map3k1 loss-of-function was found to be autosomal recessive for congenital eye abnormalities, but became autosomal dominant in combination with Jnk and RhoA mutations. Additionally, Map3k1 mutation increased eye defects with an exposure to environmental agents such as dioxin. Data from eye developmental models reveal the nexus role of MAP3K1 in integrating genetic and environmental signals to control developmental activities. Here, we focus the discussions on recent advances in understanding the signaling mechanisms of MAP3K1 in eye development in mice and in sex differentiation from human genomics findings. The research works featured here lead to a deeper understanding of the in vivo signaling network, the mechanisms of gene–environment interactions, and the relevance of this multifaceted protein kinase in disease etiology and pathogenesis.

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A cryptic tubulin-binding domain links MEKK1 to curved tubulin protomers

Cited by 13 publications

References 96 publications

Transcription level differences in Taxus wallichiana var. mairei elicited by Ce3+, Ce4+ and methyl jasmonate

Transcription level differences in Taxus wallichiana var. mairei elicited by Ce3+, Ce4+ and methyl jasmonate

The Microtubule-Targeting Agent Pretubulysin Impairs the Inflammatory Response in Endothelial Cells by a JNK-Dependent Deregulation of the Histone Acetyltransferase Brd4

Genetic Control of MAP3K1 in Eye Development and Sex Differentiation

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