DUB3 deubiquitinates and stabilizes NRF2 in chemotherapy resistance of colorectal cancer

Zhang, Qi; Zhang, Ze-yan; Du, Huan; Li, Shangze; Tu, Rongfu; Jia, Yifan; Zheng, Zhe; Song, Xuemin; Du, Ran; Zhang, Xiaodong

doi:10.1038/s41418-019-0303-z

Cited by 81 publications

(53 citation statements)

References 64 publications

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“…Besides CUL3-RBX1-KEAP1 complex, E3 ligase SCF β-TrCP , CUL4-DDB1-WDR23, HRD1 can also ubiquitinate NRF2 and regulate its stability [215][216][217]. DUB DUB3 removes ubiquitin chain on NRF2 and stabilize NRF2, leading to chemoresistance in colorectal cancer [218].…”

Section: Ubiquitination Of Nrf2mentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

253

178

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Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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Section: Ubiquitination Of Nrf2mentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

253

178

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“…By analyzing the expression levels of MCL1 and the other DUBs in nine ovarian cancer cell lines, we observed that only DUB3, and not USP9X or USP13, showed a significant positive correlation with MCL1, further supporting our hypothesis that DUB3 is the crucial DUB that modulates MCL1 stability 51 . Moreover, since DUB3 is a veritable oncogene due to its ability to stabilize Snail, Geminin, Cdc25A, NRF2, BRD4, and Cyclin A [87][88][89][90][91][92][93] , targeting DUB3 may be a promising strategy in cancer treatment with potentially fewer side effects.…”

Section: Dub3mentioning

confidence: 99%

Ubiquitination and deubiquitination of MCL1 in cancer: deciphering chemoresistance mechanisms and providing potential therapeutic options

Luo

Liu

2020

Cell Death Dis

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MCL1 is an important antiapoptotic member of the BCL-2 family that is distinguishable from other family members based on its relatively short half-life. Emerging studies have revealed the crucial role of MCL1 in the chemoresistance of cancer cells. The antiapoptotic function of MCL1 makes it a popular therapeutic target, although specific inhibitors have begun to emerge only recently. Notably, emerging studies have reported that several E3 ligases and deubiquitinases modulate MCL1 stability, providing an alternate means of targeting MCL1 activity. In addition, the emergence and development of proteolysis-targeting chimeras, the function of which is based on ubiquitination-mediated degradation, has shown great potential. In this review, we provide an overview of the studies investigating the ubiquitination and deubiquitination of MCL1, summarize the latest evidence regarding the development of therapeutic strategies targeting MCL1 in cancer treatment, and discuss the promising future of targeting MCL1 via the ubiquitin–proteasome system in clinical practice.

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“…The proliferation of cancer cells is suppressed upon the administration of natural anti-tumor compounds [ 19 , 20 ]. Apoptosis and cell cycle arrest can be induced via p53 up-regulation [ 21 ]. Based on the fact that poor bioavailability is one of the drawbacks of natural products, using nanoscale delivery systems can exponentially promote their anti-tumor activity against cancer cells for both in vitro and in vivo experiments [ 22 , 23 , 24 ].…”

Section: Role Of Natural Products In Cancer Therapymentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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DUB3 deubiquitinates and stabilizes NRF2 in chemotherapy resistance of colorectal cancer

Cited by 81 publications

References 64 publications

The role of ubiquitination and deubiquitination in cancer metabolism

The role of ubiquitination and deubiquitination in cancer metabolism

Ubiquitination and deubiquitination of MCL1 in cancer: deciphering chemoresistance mechanisms and providing potential therapeutic options

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

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