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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 <>
Submitted on : Friday, July 10, 2020 - 2:53:01 PM
Last modification on : Tuesday, July 21, 2020 - 1:48:12 PM
Contributor : Laurent Jonchère <>
Submitted on : Friday, July 10, 2020 - 2:53:01 PM
Last modification on : Tuesday, July 21, 2020 - 1:48:12 PM
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s41388-018-0651-z.pdf
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