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Review
. 2023 Sep 19:14:1220108.
doi: 10.3389/fendo.2023.1220108. eCollection 2023.

The roles of protein ubiquitination in tumorigenesis and targeted drug discovery in lung cancer

Zhen Ye  1   2 , Jingru Yang  1 , Hanming Jiang  2 , Xianquan Zhan  1
Affiliations
Review

The roles of protein ubiquitination in tumorigenesis and targeted drug discovery in lung cancer

Zhen Ye et al. Front Endocrinol (Lausanne). .

Abstract

The malignant lung cancer has a high morbidity rate and very poor 5-year survival rate. About 80% - 90% of protein degradation in human cells is occurred through the ubiquitination enzyme pathway. Ubiquitin ligase (E3) with high specificity plays a crucial role in the ubiquitination process of the target protein, which usually occurs at a lysine residue in a substrate protein. Different ubiquitination forms have different effects on the target proteins. Multiple short chains of ubiquitination residues modify substrate proteins, which are favorable signals for protein degradation. The dynamic balance adapted to physiological needs between ubiquitination and deubiquitination of intracellular proteins is beneficial to the health of the organism. Ubiquitination of proteins has an impact on many biological pathways, and imbalances in these pathways lead to diseases including lung cancer. Ubiquitination of tumor suppressor protein factors or deubiquitination of tumor carcinogen protein factors often lead to the progression of lung cancer. Ubiquitin proteasome system (UPS) is a treasure house for research and development of new cancer drugs for lung cancer, especially targeting proteasome and E3s. The ubiquitination and degradation of oncogene proteins with precise targeting may provide a bright prospect for drug development in lung cancer; Especially proteolytic targeted chimerism (PROTAC)-induced protein degradation technology will offer a new strategy in the discovery and development of new drugs for lung cancer.

Keywords: PROTACs; Targeted drug discovery; deubiquitination; lung cancer; ubiquitin-proteasome system; ubiquitination; ubiquitination ligase.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
E3 Ub-ligase profiling in lung cancers relative to controls. Differentially expressed E3 genes are determined with transcriptomics data between lung cancers (n =1027) and controls (n=108) from the TCGA database (fold change greater than 1 or less than -1, and p < 0.05).
Figure 2
Figure 2
Functional characteristics of differentially expressed E3 Ub-ligase genes in LC. (A) GO enrichment analysis of up-regulated E3 genes in LC group. (B) GO enrichment analysis of down-regulated E3 genes in LC group.
Figure 3
Figure 3
Functional characteristics of differentially expressed E3 Ub-ligase proteins in LC. (A) GO enrichment analysis of up-regulated E3 proteins in LC group. (B) GO enrichment analysis of down-regulated E3 proteins in LC group.
Figure 4
Figure 4
Inhibitors of the ubiquitin proteasome pathway regulate and control protein catabolism.
Figure 5
Figure 5
PROTAC mediated E3 target protein ubiquitination.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA-A Cancer J Clin (2022) 72:7–33. doi: 10.3322/caac.21708 - DOI - PubMed
    1. Torre L, Siegel R, Jemal A. Lung cancer statistics. Adv Exp Med Biol (2016) 893:1–19. doi: 10.1007/978-3-319-24223-1_1 - DOI - PubMed
    1. Hirsch F, Scagliotti G, Mulshine J, Kwon R, Curran W, Wu Y, et al. . Lung cancer: current therapies and new targeted treatments. Lancet (London England) (2017) 389:299–311. doi: 10.1016/S0140-6736(16)30958-8 - DOI - PubMed
    1. Nguyen A, Nguyen A, Dada OT, Desai PD, Ricci JC, Godbole NB, et al. . Leptomeningeal metastasis: a review of the pathophysiology, diagnostic methodology, and therapeutic landscape. Curr Oncol (Toronto Ont.) (2023) 30:5906–31. doi: 10.3390/curroncol30060442 - DOI - PMC - PubMed
    1. Goeckeritz J, Cerillo J, Sanghadia C, Hosseini M, Clark A, Pierre K, et al. . Principles of lung cancer metastasis to brain. J Skeleton System (2022) 1(1). doi: 10.58489/2836-2284/003 - DOI - PubMed

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