Bibliographic Details
| Title: |
Trauma-induced regulation of VHP-1 modulates the cellular response to mechanical stress. |
| Authors: |
Egge, Nathan, Arneaud, Sonja L. B., Fonseca, Rene Solano, Zuurbier, Kielen R., McClendon, Jacob, Douglas, Peter M. |
| Source: |
Nature Communications; 3/5/2021, Vol. 12 Issue 1, p1-18, 18p |
| Subject Terms: |
STRAINS & stresses (Mechanics), BLUNT trauma, CAENORHABDITIS elegans, CELLULAR signal transduction, MITOGEN-activated protein kinase phosphatases |
| Abstract: |
Mechanical stimuli initiate adaptive signal transduction pathways, yet exceeding the cellular capacity to withstand physical stress results in death. The molecular mechanisms underlying trauma-induced degeneration remain unclear. In the nematode C. elegans, we have developed a method to study cellular degeneration in response to mechanical stress caused by blunt force trauma. Herein, we report that physical injury activates the c-Jun kinase, KGB-1, which modulates response elements through the AP-1 transcriptional complex. Among these, we have identified a dual-specificity MAPK phosphatase, VHP-1, as a stress-inducible modulator of neurodegeneration. VHP-1 regulates the transcriptional response to mechanical stress and is itself attenuated by KGB-1-mediated inactivation of a deubiquitinase, MATH-33, and proteasomal degradation. Together, we describe an uncharacterized stress response pathway in C. elegans and identify transcriptional and post-translational components comprising a feedback loop on Jun kinase and phosphatase activity. The nervous system utilizes adaptive strategies to mitigate trauma-induced neurodegeneration. Here, the authors report that a MAPK phosphatase VHP-1 is induced by trauma and regulates transcriptional responses to mechanical stress in a C. elegans model. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
