Mechanical signals activate p38 MAPK pathway-dependent reinforcement of actin via mechanosensitive HspB1

Hoffman, Laura M.; Jensen, Christopher C.; Yoshigi, Masaaki; Beckerle, Mary C.

doi:10.1091/mbc.e17-02-0087

Cited by 69 publications

(74 citation statements)

References 98 publications

(134 reference statements)

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“…HspB1 affects actin polymerization in vitro in a phosphorylation-dependent manner, pointing to a direct interaction (Mounier and Arrigo 2002). Mechanically stressing fibroblasts through cyclical stretch activates p38 MAPK signaling, leading to HspB1 phosphorylation and its recruitment to actin structures at the sites of highest traction force (Hoffman et al 2017). Similar observations of recruitment to actin fibers have been reported for HspB5, through testing the effects of heat stress (Singh et al 2007;Yin et al 2019).…”

Section: A Role For Shsps In Mechanical Stresssupporting

confidence: 52%

Small heat-shock proteins and their role in mechanical stress

Collier

Benesch

2020

Cell Stress and Chaperones

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The ability of cells to respond to stress is central to health. Stress can damage folded proteins, which are vulnerable to even minor changes in cellular conditions. To maintain proteostasis, cells have developed an intricate network in which molecular chaperones are key players. The small heat-shock proteins (sHSPs) are a widespread family of molecular chaperones, and some sHSPs are prominent in muscle, where cells and proteins must withstand high levels of applied force. sHSPs have long been thought to act as general interceptors of protein aggregation. However, evidence is accumulating that points to a more specific role for sHSPs in protecting proteins from mechanical stress. Here, we briefly introduce the sHSPs and outline the evidence for their role in responses to mechanical stress. We suggest that sHSPs interact with mechanosensitive proteins to regulate physiological extension and contraction cycles. It is likely that further study of these interactionsenabled by the development of experimental methodologies that allow protein contacts to be studied under the application of mechanical forcewill expand our understanding of the activity and functions of sHSPs, and of the roles played by chaperones in general.

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Section: A Role For Shsps In Mechanical Stresssupporting

confidence: 52%

Small heat-shock proteins and their role in mechanical stress

Collier

Benesch

2020

Cell Stress and Chaperones

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“…MK2 deletion phenotypes range from defects in immediate early gene responses over impaired cytokine production and regulation of apoptosis and/or necroptosis to non-coding RNA regulation and defects in migration. They could be linked to specific substrates of MK2, such as TTP and SRF (Ronkina et al, 2011), as well as RIPK1 (Dondelinger et al, 2017;Jaco et al, 2017;Menon et al, 2017), RBM7 (Blasius et al, 2014;Tiedje et al, 2015), and Hsp25/27 (Hoffman et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Alternative Translation Initiation Generates a Functionally Distinct Isoform of the Stress-Activated Protein Kinase MK2

et al. 2019

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Graphical Abstract Highlights d The MK2 mRNA contains an in-frame upstream CUG translation initiation site d An N-terminal extended isoform of the protein kinase MK2 is consequently translated d This isoform has unique and shared properties compared to the canonical isoform d The extended N terminus of long MK2 is phosphorylated at a defined serine residue SUMMARYAlternative translation is an important mechanism of post-transcriptional gene regulation leading to the expression of different protein isoforms originating from the same mRNA. Here, we describe an abundant long isoform of the stress/p38 MAPK -activated protein kinase MK2. This isoform is constitutively translated from an alternative CUG translation initiation start site located in the 5 0 UTR of its mRNA. The RNA helicase eIF4A1 is needed to ensure translation of the long and the known short isoforms of MK2, of which the molecular properties were determined. Only the short isoform phosphorylated Hsp27 in vivo, supported migration and stress-induced immediate early gene (IEG) expression. Interaction profiling revealed short-isoform-specific binding partners that were associated with migration. In contrast, the long isoform contains at least one additional phosphorylatable serine in its unique N terminus. In sum, our data reveal a longer isoform of MK2 with distinct physiological properties.

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“…46,47 It has been shown that the action of 2HD causes a cytoskeleton reorganization, which is expressed in F-actin redistribution, a change in the number and type of filopodia and fibrils (Figure 3), leading to cell shape changes, decrease in intercellular contacts and monolayer rarefaction (Figure 2). It is known that the state of the cell cytoskeleton can change with activation of MAPK cascades, including JNK and p38 MAPK.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that the state of the cell cytoskeleton can change with activation of MAPK cascades, including JNK and p38 MAPK. 46,47 It has been shown that the action of 2HD causes a cytoskeleton reorganization, which is expressed in F-actin redistribution, a change in the number and type of filopodia and fibrils (Figure 3…”

Section: Discussionmentioning

confidence: 99%

2‐Hexadecenal inhibits growth of C6 glioma cells

Семенкова

Kvacheva

Lisovskaya

et al. 2019

Cell Biochemistry & Function

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2-Hexadecenal (2HD) formation in the organism occurs via irreversible enzymatic degradation of sphingosine-1-phosphate or nonenzymatic γ-, UV-, or HOCl-induced destruction of a number of sphingolipids including S1P. The current research focuses on the study of 2HD effects on C6 glioma cells growth. The results obtained show that 2HD causes a dose-dependent decrease in proliferative and mitotic indices.The change in the mitotic index is due to the redistribution of cells in the different phases of mitosis. These processes are accompanied by cytoskeleton rearrangement and changes in cell morphology, which are expressed in F-actin redistribution, change in the number and type of filopodia and fibrils, leading to cell shape changes, decrease in intercellular contacts and monolayer rarefaction. Cells treatment with 2HD leads to apoptosis induction and signalling pathways modification, including activation of JNK, p38, and ERK1/2 MAPK but not PI3K. The effects observed are not related to the cytotoxicity of 2HD. Significance of the study: 2HD-an unsaturated aldehyde, which level can rise under conditions of oxidative stress as a result of nonenzymatic sphingolipids' destruction. The mechanisms of 2HD action on various cell types have not been sufficiently studied. Therefore, the study on functional role of this aldehyde in different cell types that may be its target is relevant. This study demonstrated that 2HD inhibits growth of C6 glioma cells due to modification of intracellular processes of signal transduction, cytoskeleton rearrangement, change in the mitotic regimen and apoptosis induction.

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Mechanical signals activate p38 MAPK pathway-dependent reinforcement of actin via mechanosensitive HspB1

Cited by 69 publications

References 98 publications

Small heat-shock proteins and their role in mechanical stress

Small heat-shock proteins and their role in mechanical stress

Alternative Translation Initiation Generates a Functionally Distinct Isoform of the Stress-Activated Protein Kinase MK2

2‐Hexadecenal inhibits growth of C6 glioma cells

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