Targeting ubiquitin signaling for cancer immunotherapy

Zhou, Xiaofei; Sun, Shao‐Cong

doi:10.1038/s41392-020-00421-2

Cited by 44 publications

(40 citation statements)

References 234 publications

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“…In 2019, PROTAC ARV-110, which targets the androgen receptor (AR) for degradation in prostate cancer, has been approved by the FDA for phase I clinical trials (Neklesa et al, 2017;Pettersson and Crews, 2019;Schapira et al, 2019;Ding et al, 2020;Poh, 2020;Wang et al, 2020a). Development of novel therapies by targeting the ubiquitin system (DUBs/E3s inhibitors or PROTACs) on ferroptosis-related proteins may facilitate the clinical application of ferroptosis in the future (Popovic et al, 2014;Zhou and Sun, 2021).…”

Section: Targeting Ubiquitination For Ferroptosis In Cancer Therapymentioning

confidence: 99%

Regulation of Ferroptosis Pathway by Ubiquitination

Wang

et al. 2021

Front. Cell Dev. Biol.

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Ferroptosis is an iron-dependent form of programmed cell death, which plays crucial roles in tumorigenesis, ischemia–reperfusion injury and various human degenerative diseases. Ferroptosis is characterized by aberrant iron and lipid metabolisms. Mechanistically, excess of catalytic iron is capable of triggering lipid peroxidation followed by Fenton reaction to induce ferroptosis. The induction of ferroptosis can be inhibited by sufficient glutathione (GSH) synthesis via system Xc– transporter-mediated cystine uptake. Therefore, induction of ferroptosis by inhibition of cystine uptake or dampening of GSH synthesis has been considered as a novel strategy for cancer therapy, while reversal of ferroptotic effect is able to delay progression of diverse disorders, such as cardiopathy, steatohepatitis, and acute kidney injury. The ubiquitin (Ub)–proteasome pathway (UPP) dominates the majority of intracellular protein degradation by coupling Ub molecules to the lysine residues of protein substrate, which is subsequently recognized by the 26S proteasome for degradation. Ubiquitination is crucially involved in a variety of physiological and pathological processes. Modulation of ubiquitination system has been exhibited to be a potential strategy for cancer treatment. Currently, more and more emerged evidence has demonstrated that ubiquitous modification is involved in ferroptosis and dominates the vulnerability to ferroptosis in multiple types of cancer. In this review, we will summarize the current findings of ferroptosis surrounding the viewpoint of ubiquitination regulation. Furthermore, we also highlight the potential effect of ubiquitination modulation on the perspective of ferroptosis-targeted cancer therapy.

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Section: Targeting Ubiquitination For Ferroptosis In Cancer Therapymentioning

confidence: 99%

Regulation of Ferroptosis Pathway by Ubiquitination

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…The multiple steps of metastasis rely on reciprocal interactions between breast cancer cells and the microenvironment. Immune cells and their mediators are known to facilitate metastasis within the microenvironment (126). Natural killer (NK) cells play an essential role in the defense against viruses or microbial pathogens and malignancies produced by the body itself.…”

Section: Immunity Response/rescuementioning

confidence: 99%

E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications

et al. 2021

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Female breast cancer has become the most commonly occurring cancer worldwide. Although it has a good prognosis under early diagnosis and appropriate treatment, breast cancer metastasis drastically causes mortality. The process of metastasis, which includes cell epithelial–mesenchymal transition, invasion, migration, and colonization, is a multistep cascade of molecular events directed by gene mutations and altered protein expressions. Ubiquitin modification of proteins plays a common role in most of the biological processes. E3 ubiquitin ligase, the key regulator of protein ubiquitination, determines the fate of ubiquitinated proteins. E3 ubiquitin ligases target a broad spectrum of substrates. The aberrant functions of many E3 ubiquitin ligases can affect the biological behavior of cancer cells, including breast cancer metastasis. In this review, we provide an overview of these ligases, summarize the metastatic processes in which E3s are involved, and comprehensively describe the roles of E3 ubiquitin ligases. Furthermore, we classified E3 ubiquitin ligases based on their structure and analyzed them with the survival of breast cancer patients. Finally, we consider how our knowledge can be used for E3s’ potency in the therapeutic intervention or prognostic assessment of metastatic breast cancer.

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“…Due to its critical role in infection initiation, spike protein has been considered as topmost target of neutralizing antibodies and drug molecules [3] . However, changes in the genome (genetic material) sequence due to mutation in different region of spike protein reduces the efficacy of existing vaccines and antiviral drugs which were developed for parent virus [4,5] . New variants may not behave as the previously characterized sequence (wild type/preexisting mutants) against recognizing markers/vaccines/therapeutics and may escape from diagnostic tests, immune system, therapeutic drugs [4–11] …”

Section: Introductionmentioning

confidence: 99%

“…[ 4 , 5 ] New variants may not behave as the previously characterized sequence (wild type/preexisting mutants) against recognizing markers/vaccines/therapeutics and may escape from diagnostic tests, immune system, therapeutic drugs. [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]…”

Section: Introductionmentioning

confidence: 99%

Molecular Level Dissection of Critical Spike Mutations in SARS‐CoV‐2 Variants of Concern (VOCs): A Simplified Review

2021

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SARS-CoV-2 virus during its spread in the last one and half year has picked up critical changes in its genetic code i.e. mutations, which have leads to deleterious epidemiological characteristics. Due to critical role of spike protein in cell entry and pathogenesis, mutations in spike regions have been reported to enhance transmissibility, disease severity, possible escape from vaccine-induced immune response and reduced diagnostic sensitivity/specificity. Considering the structure-function impact of mutations, understanding the molecular details of these key mutations of newly emerged variants/lineages is of urgent concern. In this review, we have explored the literature on key spike mutations harbored by alpha, beta, gamma and delta 'variants of concern' (VOCs) and discussed their molecular consequences in the context of resultant virus biology.

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Targeting ubiquitin signaling for cancer immunotherapy

Cited by 44 publications

References 234 publications

Regulation of Ferroptosis Pathway by Ubiquitination

Regulation of Ferroptosis Pathway by Ubiquitination

E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications

Molecular Level Dissection of Critical Spike Mutations in SARS‐CoV‐2 Variants of Concern (VOCs): A Simplified Review

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