Imperial College London
Alternate

DrValentinaCaputo

Faculty of Medicine, Department of Immunology and Inflammation

Honorary Research Fellow
 
 
 
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Contact

 

v.caputo

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Parzych:2019:10.1038/s41388-018-0651-z,
author = {Parzych, K and Saavedra, Garcia P and Valbuena, G and Alsadah, HAH and Robinson, M and Penfold, L and Kuzeva, D and Ruiz, Tellez A and Loaiza, S and Holzmann, V and Caputo, V and Johnson, DC and Kaiser, MF and Karadimitris, A and Lam, E and Chevet, E and Feldhahn, N and Keun, H and Auner, H},
doi = {10.1038/s41388-018-0651-z},
journal = {Oncogene},
pages = {3216--3231},
title = {The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation},
url = {http://dx.doi.org/10.1038/s41388-018-0651-z},
volume = {38},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Parzych,K
AU  - Saavedra,Garcia P
AU  - Valbuena,G
AU  - Alsadah,HAH
AU  - Robinson,M
AU  - Penfold,L
AU  - Kuzeva,D
AU  - Ruiz,Tellez A
AU  - Loaiza,S
AU  - Holzmann,V
AU  - Caputo,V
AU  - Johnson,DC
AU  - Kaiser,MF
AU  - Karadimitris,A
AU  - Lam,E
AU  - Chevet,E
AU  - Feldhahn,N
AU  - Keun,H
AU  - Auner,H
DO  - 10.1038/s41388-018-0651-z
EP  - 3231
PY  - 2019///
SN  - 0950-9232
SP  - 3216
TI  - The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/s41388-018-0651-z
UR  - http://hdl.handle.net/10044/1/66733
VL  - 38
ER  -
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