Guanylate-binding Protein 1 Modulates Proteasomal Machinery in Ovarian Cancer

Overview

Journal iScience

Publisher Cell Press

Date 2023 Nov 29

PMID 38026225

Authors

Dhanir Tailor

Fernando Jose Garcia-Marques

Abel Bermudez

Sharon J Pitteri

Sanjay V Malhotra

Affiliations

Soon will be listed here.

Abstract

Guanylate-binding protein 1 (GBP1) is known as an interferon-γ-induced GTPase. Here, we used genetically modified ovarian cancer (OC) cells to study the role of GBP1. The data generated show that GBP1 inhibition constrains the clonogenic potential of cancer cells. studies revealed that GBP1 overexpression in tumors promotes tumor progression and reduces median survival, whereas GBP1 inhibition delayed tumor progression with longer median survival. We employed proteomics-based thermal stability assay (CETSA) on GBP1 knockdown and overexpressed OC cells to study its molecular functions. CETSA results show that GBP1 interacts with many members of the proteasome. Furthermore, GBP1 inhibition sensitizes OC cells to paclitaxel treatment via accumulated ubiquitinylated proteins where GBP1 inhibition decreases the overall proteasomal activity. In contrast, GBP1-overexpressing cells acquired paclitaxel resistance via boosted cellular proteasomal activity. Overall, these studies expand the role of GBP1 in the activation of proteasomal machinery to acquire chemoresistance.

Citing Articles

Newcastle disease virus promotes pyroptosis in medulloblastoma cells by regulating interferon-gamma-mediated guanylate-binding protein 1 expression and activating caspase-4.

Ren P, Yu J, Wang D, Zeng L, Zhang X, Liu X Cytojournal. 2024; 21:39.

PMID: 39563668 PMC: 11574683. DOI: 10.25259/Cytojournal_39_2024.

References

Fukumoto M, Amanuma T, Kuwahara Y, Shimura T, Suzuki M, Mori S . Guanine nucleotide-binding protein 1 is one of the key molecules contributing to cancer cell radioresistance. Cancer Sci. 2014; 105(10):1351-9. PMC: 4462352. DOI: 10.1111/cas.12489. View

Mateus A, Kurzawa N, Becher I, Sridharan S, Helm D, Stein F . Thermal proteome profiling for interrogating protein interactions. Mol Syst Biol. 2020; 16(3):e9232. PMC: 7057112. DOI: 10.15252/msb.20199232. View

Frankowska N, Lisowska K, Witkowski J . Proteolysis dysfunction in the process of aging and age-related diseases. Front Aging. 2022; 3:927630. PMC: 9361021. DOI: 10.3389/fragi.2022.927630. View

Fisch D, Bando H, Clough B, Hornung V, Yamamoto M, Shenoy A . Human GBP1 is a microbe-specific gatekeeper of macrophage apoptosis and pyroptosis. EMBO J. 2019; 38(13):e100926. PMC: 6600649. DOI: 10.15252/embj.2018100926. View

Soave C, Guerin T, Liu J, Dou Q . Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing. Cancer Metastasis Rev. 2017; 36(4):717-736. PMC: 5722705. DOI: 10.1007/s10555-017-9705-x. View

Gama V, Swahari V, Schafer J, Kole A, Evans A, Huang Y . The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells. Sci Signal. 2014; 7(334):ra67. PMC: 4182917. DOI: 10.1126/scisignal.2005309. View

Tyanova S, Temu T, Cox J . The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat Protoc. 2016; 11(12):2301-2319. DOI: 10.1038/nprot.2016.136. View

Komarova N, Wodarz D . Drug resistance in cancer: principles of emergence and prevention. Proc Natl Acad Sci U S A. 2005; 102(27):9714-9. PMC: 1172248. DOI: 10.1073/pnas.0501870102. View

Cheng L, Gou L, Wei T, Zhang J . GBP1 promotes erlotinib resistance via PGK1‑activated EMT signaling in non‑small cell lung cancer. Int J Oncol. 2020; 57(3):858-870. DOI: 10.3892/ijo.2020.5086. View

10.

Lanczky A, Gyorffy B . Web-Based Survival Analysis Tool Tailored for Medical Research (KMplot): Development and Implementation. J Med Internet Res. 2021; 23(7):e27633. PMC: 8367126. DOI: 10.2196/27633. View

11.

Manasanch E, Orlowski R . Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol. 2017; 14(7):417-433. PMC: 5828026. DOI: 10.1038/nrclinonc.2016.206. View

12.

Ming H, Li B, Jiang J, Qin S, Nice E, He W . Protein degradation: expanding the toolbox to restrain cancer drug resistance. J Hematol Oncol. 2023; 16(1):6. PMC: 9872387. DOI: 10.1186/s13045-023-01398-5. View

13.

Navarro P, Trevisan-Herraz M, Bonzon-Kulichenko E, Nunez E, Martinez-Acedo P, Perez-Hernandez D . General statistical framework for quantitative proteomics by stable isotope labeling. J Proteome Res. 2014; 13(3):1234-47. DOI: 10.1021/pr4006958. View

14.

Ledermann J, Kristeleit R . Optimal treatment for relapsing ovarian cancer. Ann Oncol. 2010; 21 Suppl 7:vii218-22. DOI: 10.1093/annonc/mdq377. View

15.

Enenkel C, Kang R, Wilfling F, Ernst O . Intracellular localization of the proteasome in response to stress conditions. J Biol Chem. 2022; 298(7):102083. PMC: 9218506. DOI: 10.1016/j.jbc.2022.102083. View

16.

Hernandez-Vargas H, von Kobbe C, Sanchez-Estevez C, Julian-Tendero M, Palacios J, Moreno-Bueno G . Inhibition of paclitaxel-induced proteasome activation influences paclitaxel cytotoxicity in breast cancer cells in a sequence-dependent manner. Cell Cycle. 2007; 6(21):2662-8. DOI: 10.4161/cc.6.21.4821. View

17.

Guenzi E, Topolt K, Cornali E, Jorg A, Matzen K, Zietz C . The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokines. EMBO J. 2001; 20(20):5568-77. PMC: 125279. DOI: 10.1093/emboj/20.20.5568. View

18.

Chen L, Madura K . Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Cancer Res. 2005; 65(13):5599-606. DOI: 10.1158/0008-5472.CAN-05-0201. View

19.

Honkala A, Tailor D, V Malhotra S . Guanylate-Binding Protein 1: An Emerging Target in Inflammation and Cancer. Front Immunol. 2020; 10:3139. PMC: 7025589. DOI: 10.3389/fimmu.2019.03139. View

20.

Schmidt M, Gan Z, Komander D, Dewson G . Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities. Cell Death Differ. 2021; 28(2):570-590. PMC: 7862249. DOI: 10.1038/s41418-020-00706-7. View