 |
 |
 |
Journal articles
The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation
Abstract : VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence that VCP/p97 acts as a regulator of cellular metabolism. We found that VCP/p97 was tied to multiple metabolic processes on the gene expression level in a diverse range of cancer cell lines and in patient-derived multiple myeloma cells. Cellular VCP/p97 dependency to maintain proteostasis was increased under conditions of glucose and glutamine limitation in a range of cancer cell lines from different tissues. Moreover, glutamine depletion led to increased VCP/p97 expression, whereas VCP/p97 inhibition perturbed metabolic processes and intracellular amino acid turnover. GCN2, an amino acid-sensing kinase, attenuated stress signalling and cell death triggered by VCP/p97 inhibition and nutrient shortages and modulated ERK activation, autophagy, and glycolytic metabolite turnover. Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein homoeostasis.
Cited literature [86 references]
https://hal-univ-rennes1.archives-ouvertes.fr/hal-02020889
Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Friday, July 10, 2020 - 2:53:01 PM
Last modification on : Tuesday, January 18, 2022 - 2:26:07 PM
Long-term archiving on: : Monday, November 30, 2020 - 8:21:40 PM
Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Friday, July 10, 2020 - 2:53:01 PM
Last modification on : Tuesday, January 18, 2022 - 2:26:07 PM
Long-term archiving on: : Monday, November 30, 2020 - 8:21:40 PM
File
s41388-018-0651-z.pdf
Publication funded by an institution