USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM

Wu, Chenming; Chang, Yi-Ming; Chen, Junliang; Su, Yang; Li, Lei; Chen, Yuping; Li, Yunhui; Wu, Jing; Huang, Jinzhou; Zhao, Fei; Wang, Wenrui; Yin, Hui; Wang, Shunli; Jin, Mingpeng; Lou, Zhenkun; Zhu, Weiguo; Luo, Kuntian; Zhang, Jie; Yuan, Jian

doi:10.1093/nar/gkab842

Cited by 16 publications

(16 citation statements)

References 75 publications

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“…In recent years, DDR pathway has attracted more and more attention from clinical medicine and translational medicine due to its driving role in tumor genesis and guiding role in tumor precision therapy. DDR pathway has been extensively studied in breast cancer 19 , ovarian cancer 20 , prostate cancer 21 , pancreatic cancer 22 and other cancers, while its guiding significance in the diagnosis and treatment of liver cancer remains to be further clarified.…”

Section: Discussionmentioning

confidence: 99%

Analysis of mutations in DNA damage repair pathway gene in Chinese patients with hepatocellular carcinoma

Azhar

et al. 2022

Sci Rep

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The incidence of hepatocellular carcinoma (HCC) has increased in these years. DNA damage repair (DDR) pathway is required in response to DNA damage Gene mutations in DDR pathway play an important role in different stages of tumorigenesis and development. Based on the importance of DDR pathway in precision therapy of multiple cancers, we analyzed DDR gene mutations in Chinese patients with HCC. The results showed that (tumor mutation burden) TMB was significantly higher in HCC patients who carried somatic mutations in DDR than in non-carriers, and TMB in patients with DS, MMR mutations and DDR genes mutations such as RAD50, MLH1, MSH2, CHEK2 was significantly higher than that in wild-type patients. Based on the results of next-generation sequencing (NGS) testing, we are trying to provide clues for targeted therapy and provide feasible basis for PD-1/PD-L1 immune checkpoint inhibitor therapy.

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Section: Discussionmentioning

confidence: 99%

Analysis of mutations in DNA damage repair pathway gene in Chinese patients with hepatocellular carcinoma

Azhar

et al. 2022

Sci Rep

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“…It was also demonstrated that CYLD promotes necroptosis after deubiquitination of RIP1 in necrosomes 38,43 . USP37 can regulate BLM RecQ like helicase deubiquitination and stabilises its expression, thereby maintaining the DNA damage response in BC cells 44 . Sun found that USP36 deubiquitinates c‐Myc in the nucleolus and acts downstream of c‐Myc to promote BC proliferation 45 .…”

Section: Discussionmentioning

confidence: 99%

Deubiquitinase USP19 modulates apoptotic calcium release and endoplasmic reticulum stress by deubiquitinating BAG6 in triple negative breast cancer

Zhang,

Chen,

Qian

et al. 2023

Clinical & Translational Med

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BackgroundTriple‐negative breast cancer (TNBC), a heterogeneous subtype of breast cancer (BC), had poor prognosis. Endoplasmic reticulum (ER) stress was responsible for cellular processes and played a crucial role in the cell function. ER stress is a complex and dynamic process that can induce abnormal apoptosis and death. However, the underlying mechanism of ER stress involved in TNBC is not well defined.MethodsWe identified ubiquitin‐specific protease 19 (USP19) as a TNBC negative regulator for further investigation. The effects of USP19 on BC proliferation were assessed in vitro using proliferation test and cell‐cycle assays, while the effects in vivo were examined using a mouse tumorigenicity model. Through in vitro flow cytometric analyses and in vivo TUNEL assays, cell apoptosis was assessed. Proteomics was used to examine the proteins that interact with USP19.ResultsMultiple in vitro and in vivo tests showed that USP19 decreases TNBC cell growth while increasing apoptosis. Then, we demonstrated that USP19 interacts with deubiquitinates and subsequently stabilises family molecular chaperone regulator 6 (BAG6). BAG6 can boost B‐cell lymphoma 2 (BCL2) ubiquitination and degradation, thereby raising ER calcium (Ca2+) levels and causing ER stress. We also found that the N6‐methyladenosine (m6A) “writer” methyltransferase‐like 14 (METTL14) increased global m6A modification.ConclusionsOur study reveals that USP19 elevates the intracellular Ca2+ concentration to alter ER stress via regulation of BAG6 and BCL2 stability and may be a viable therapeutic target for TNBC therapy.

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“… 43 Besides, USP37 was also demonstrated to deubiquitinate and stabilize BLM, a human RecQ helicase, further sustaining the DNA damage response (DDR) and resulting in chemotherapy resistance. 44 …”

Section: Discussionmentioning

confidence: 99%

Stabilization of estrogen receptor α by USP37 contributes to the progression of breast cancer

Cao

Wang

et al. 2023

Cancer Science

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Breast cancer is a major cause of cancer‐related morbidity and mortality in women. Estrogen receptor‐positive breast cancer accounts for roughly 70%‐80% of breast tumors, and estrogen receptor alpha (ERα) has been considered as a key driver in promoting breast cancer progression. In the present study, we identified USP37 as a novel modulator in modulating ERα ubiquitination and stability. The expression of USP37 was upregulated in ERα‐positive breast cancer and correlated with ERα protein level. High expression of USP37 was associated with unfavorable prognosis. USP37 depletion resulted in significantly decreased ERα protein level, ERα target genes expression as well as the estrogen response element activity in breast cancer cells. Further mechanistic study revealed the interaction between USP37 and ERα: USP37 regulated ERα signaling through modulating protein stability instead of gene expression, in which it stabilized ERα protein via inhibiting the K48‐specific polyubiquitination process. Additionally, USP37 depletion led to growth inhibition and cell cycle arrest of ERα‐positive breast cancer cells, which could be further rescued by ERα overexpression. Overall, our study proposed a novel post‐translational mechanism of ERα in promoting breast cancer progression. Targeting USP37 may be proved to be a promising strategy for patients with ERα‐positive breast cancer.

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USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM

Cited by 16 publications

References 75 publications

Analysis of mutations in DNA damage repair pathway gene in Chinese patients with hepatocellular carcinoma

Analysis of mutations in DNA damage repair pathway gene in Chinese patients with hepatocellular carcinoma

Deubiquitinase USP19 modulates apoptotic calcium release and endoplasmic reticulum stress by deubiquitinating BAG6 in triple negative breast cancer

Stabilization of estrogen receptor α by USP37 contributes to the progression of breast cancer

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