Targeting CSC-related transcription factors by E3 ubiquitin ligases for cancer therapy

Wang, Weijia; Liu, Wenjun; Chen, Qiuli; Yuan, Yong

doi:10.1016/j.semcancer.2022.11.002

Cited by 24 publications

(12 citation statements)

References 215 publications

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“…The E3s SKP2, Fbw7, β-TrCP1, CHIP and FBXO32 promote c-Myc ubiquitination-mediated proteasomal degradation, thereby inhibiting tumorigenesis. In contrast, USP37- and USP36-mediated deubiquitination can promote tumorigenesis by stabilizing c-Myc [ 113 , 160 ]. Therefore, the activation of c-Myc E3s or inhibition of c-Myc DUBs may have therapeutic implications in cancer.…”

Section: Developing Strategies To Target Ubiquitination In Cancer The...mentioning

confidence: 99%

Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy

Spano,

Catara

2023

Cells

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Ubiquitination is a reversible post-translational modification based on the chemical addition of ubiquitin to proteins with regulatory effects on various signaling pathways. Ubiquitination can alter the molecular functions of tagged substrates with respect to protein turnover, biological activity, subcellular localization or protein–protein interaction. As a result, a wide variety of cellular processes are under ubiquitination-mediated control, contributing to the maintenance of cellular homeostasis. It follows that the dysregulation of ubiquitination reactions plays a relevant role in the pathogenic states of human diseases such as neurodegenerative diseases, immune-related pathologies and cancer. In recent decades, the enzymes of the ubiquitin–proteasome system (UPS), including E3 ubiquitin ligases and deubiquitinases (DUBs), have attracted attention as novel druggable targets for the development of new anticancer therapeutic approaches. This perspective article summarizes the peculiarities shared by the enzymes involved in the ubiquitination reaction which, when deregulated, can lead to tumorigenesis. Accordingly, an overview of the main pharmacological interventions based on targeting the UPS that are in clinical use or still in clinical trials is provided, also highlighting the limitations of the therapeutic efficacy of these approaches. Therefore, various attempts to circumvent drug resistance and side effects as well as UPS-related emerging technologies in anticancer therapeutics are discussed.

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Section: Developing Strategies To Target Ubiquitination In Cancer The...mentioning

confidence: 99%

Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy

Spano,

Catara

2023

Cells

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“…They act as a bridge between the E2 enzyme and the substrate, ensuring accurate ubiquitin transfer. The E3 ligases are primarily responsible for the specificity of ubiquitination, determining which proteins will be tagged for various fates, including degradation, localization, or involvement in various cellular processes ( 35 ). There are several types of E3 ligases, categorized mainly based on their mechanism of action and structural features.…”

Section: Introductionmentioning

confidence: 99%

PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy

Ren,

Wang,

Liu

et al. 2024

Front. Immunol.

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Immunotherapy has been developed, which harnesses and enhances the innate powers of the immune system to fight disease, particularly cancer. PD-1 (programmed death-1) and PD-L1 (programmed death ligand-1) are key components in the regulation of the immune system, particularly in the context of cancer immunotherapy. PD-1 and PD-L1 are regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation and glycosylation. PROTACs (Proteolysis Targeting Chimeras) are a type of new drug design technology. They are specifically engineered molecules that target specific proteins within a cell for degradation. PROTACs have been designed and demonstrated their inhibitory activity against the PD-1/PD-L1 pathway, and showed their ability to degrade PD-1/PD-L1 proteins. In this review, we describe how PROTACs target PD-1 and PD-L1 proteins to improve the efficacy of immunotherapy. PROTACs could be a novel strategy to combine with radiotherapy, chemotherapy and immunotherapy for cancer patients.

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“…1 C). It is indicated that ubiquitination participates in mediating the transcriptional regulatory network with CSCs and EMT, E3 ubiquitin ligase can modulate the expression level of these pluripotent TFs by ubiquitination alone or ubiquitination combined degradation [ 123 ]. Due to the undruggable property of TFs, it is shown that targeting ubiquitin proteasome system (UPS) to inhibit the TFs expression is a potential alternative strategy [ 124 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies

Zhang,

Zhang

2024

J Exp Clin Cancer Res

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Cancer stem cells (CSCs) were first discovered in the 1990s, revealing the mysteries of cancer origin, migration, recurrence and drug-resistance from a new perspective. The expression of pluripotent genes and complex signal regulatory networks are significant features of CSC, also act as core factors to affect the characteristics of CSC. Transcription is a necessary link to regulate the phenotype and potential of CSC, involving chromatin environment, nucleosome occupancy, histone modification, transcription factor (TF) availability and cis-regulatory elements, which suffer from ambient pressure. Especially, the expression and activity of pluripotent TFs are deeply affected by both internal and external factors, which is the foundation of CSC transcriptional regulation in the current research framework. Growing evidence indicates that regulating epigenetic modifications to alter cancer stemness is effective, and some special promoters and enhancers can serve as targets to influence the properties of CSC. Clarifying the factors that regulate CSC transcription will assist us directly target key stem genes and TFs, or hinder CSC transcription through environmental and other related factors, in order to achieve the goal of inhibiting CSC and tumors. This paper comprehensively reviews the traditional aspects of transcriptional regulation, and explores the progress and insights of the impact on CSC transcription and status through tumor microenvironment (TME), hypoxia, metabolism and new meaningful regulatory factors in conjunction with the latest research. Finally, we present opinions on omnidirectional targeting CSCs transcription to eliminate CSCs and address tumor resistance.

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Targeting CSC-related transcription factors by E3 ubiquitin ligases for cancer therapy

Cited by 24 publications

References 215 publications

Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy

Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy

PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy

Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies

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