USP35, regulated by estrogen and AKT, promotes breast tumorigenesis by stabilizing and enhancing transcriptional activity of estrogen receptor α

Cao, Jianhua; Wu, Du; Wu, Guang; Wang, Yaqi; Ren, Tianhao; Wang, Yang; Lv, Yingshuai; Wei, Sun; Wang, Jieyi; Qian, Changrui; He, Licai; Yang, Kaiyan; Li, Hongzhi; Gu, Haihua

doi:10.1038/s41419-021-03904-4

Cited by 15 publications

(12 citation statements)

References 43 publications

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“…Besides, deubiquitinase USP35 could restrain STING-mediated interferon signaling in ovarian cancer, highlighting the potential associations between USP35 and CD8 + T cell infiltrations [ 20 ]. Moreover, AKT-activated USP35 enhanced ERα stability by interacting and deubiquitinating ERα, suggesting that USP35 may be a therapeutical vulnerability for ER + breast cancer with endocrine resistance [ 21 ]. Considering USP35 correlates tightly with tumor progression, whether USP35 could modulate other oncogenic features, like metabolic remodeling, stem-like properties is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis

et al. 2022

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The mutual interplay between epigenetic modifications and metabolic rewiring contributes to malignant features of prostate adenocarcinoma (PRAD). This study aimed to uncover the biological roles of deubiquitylase USP35 in PRAD and find effective epigenetic or metabolic targets. Bioinformatic tools or methods revealed that USP35 is upregulated in PRAD samples and correlates with inferior prognosis. The in vitro and in vivo assays suggested that USP35 could enhance malignant features of PRAD cells. Mechanistically, we found that USP35 could directly deubiquitinate and stabilize BRPF1 proteins. USP35 depends on accumulated BRPF1 proteins to accelerate cell growth, stem-like properties, and migration in vitro and in vivo. Interestingly, high BRPF1 could bind to promoter of SREBP2 and activate the SREBP2 transcriptional capacity. Therefore, USP35/BRPF1 aixs could promote expressions of mevalonate (MVA) metabolism signature in a SREBP2-dependent manner. USP35 depends on BRPF1 to maintain the activity of mevalonate metabolism in PRAD cells. Last of all, we observed that targeting BRPF1 or using MVA inhibitor (atorvastatin) are effective to suppress USP35high PRAD in vivo tumor growth. USP35 is an indicator of MVA metabolic signature in PRAD. Collectively, our study highlighted the USP35/BRPF1/SREBP2 axis in modulating MVA metabolism in PRAD, suggesting the significance of BRPF1 or MVA as the potential therapeutic targets for PRAD treatment.

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Section: Discussionmentioning

confidence: 99%

Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis

et al. 2022

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“…ERα has been shown to be a substrate of deubiquitinase (Pesiri et al, 2016). A few DUBs exert their pro-oncogenic function by triggering ERα deubiquitination to maintain the stability of ERα in BCa (Cao et al, 2021; Tang et al, 2021; Wang et al, 2020; Xia et al, 2021; Xia et al, 2019). Furthermore, DUB inhibitors targeting USP14 and UCHL5 downregulate ERα expression and induce cancer cell apoptosis, providing a prospective strategy for ER-positive BCa treatment (Xia et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

MYSM1 co-activates ERα action via histone and non-histone deubiquitination to confer antiestrogen resistance in breast cancer

Zhao

Luan

Sun

et al. 2022

Preprint

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Endocrine resistance is a crucial challenge in estrogen receptor alpha (ERα)-positive breast cancer (BCa) therapy. Aberrant alteration in modulation of E2/ERα signaling pathway has emerged as the putative contributor for endocrine resistance in BCa. Thus, identification the efficient ERα cofactor remains necessary for finding a potential therapeutic target for endocrine resistance. Herein, we have demonstrated that Myb like, SWIRM and MPN domains 1 (MYSM1) as a histone deubiquitinase is a novel ERα co-activator with established Drosophila experimental model. Our results showed that MYSM1 participated in up-regulation of ERα action via histone and non-histone deubiquitination. We provided the evidence to show that MYSM1 was involved in maintenance of ERα stability via ERα deubiquitination. Furthermore, silencing MYSM1 induced enhancement of histone H2A ubiquitination as well as reduction of histone H3K4me3 and H3Ac levels at cis regulatory elements on promoter of ERα-regulated gene. In addition, MYSM1 depletion attenuated cell proliferation/growth in BCa-derived cell lines and xenograft models. Knockdown of MYSM1 increased the sensitivity of antiestrogen agents in BCa cells. MYSM1 was highly expressed in clinical BCa samples, especially in aromatase inhibitor (AI) non-responsive tissues. These findings clarify the molecular mechanism of MYSM1 as an epigenetic modifier in regulation of ERα action and provide a potential therapeutic target for endocrine resistance in BCa.

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“…The upregulation in USP35 seems to be not limited to HCC as other studies showed also upregulation of USP35 expression in lung, ovarian, colon adenocarcinoma, and head and neck cancer. USP35 is also involved in breast cancer progression by stabilizing and increasing transcriptional activity of estrogen receptors 35–37 …”

Section: Mitochondria‐attached Dubs Directly Involved In Mitophagymentioning

confidence: 99%

“…USP35 is also involved in breast cancer progression by stabilizing and increasing transcriptional activity of estrogen receptors. 35 , 36 , 37 …”

Section: Mitochondria‐attached Dubs Directly Involved In Mitophagymentioning

confidence: 99%

Mitochondria, mitophagy, and the role of deubiquitinases as novel therapeutic targets in liver pathology

Aryapour

Kietzmann

2022

J of Cellular Biochemistry

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Liver diseases such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC) have increased over the past few decades due to the absence or ineffective therapeutics. Recently, it has been shown that inappropriate regulation of hepatic mitophagy is linked to the pathogenesis of the above-mentioned liver diseases. As mitophagy maintains cellular homeostasis by removing damaged and nonfunctional mitochondria from the cell, the proper function of the molecules involved are of utmost importance. Thereby, mitochondrial E3 ubiquitin ligases as well as several deubiquitinases (DUBs) appear to play a unique role for the degradation of mitochondrial proteins and for proper execution of the mitophagy process by either adding or removing ubiquitin chains from target proteins. Therefore, these enzymes could be considered as valuable liver disease biomarkers and also as novel targets for therapy. In this review, we focus on the role of different DUBs on mitophagy and their contribution to NAFLD, NASH, alcohol-related liver disease, and especially HCC.

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USP35, regulated by estrogen and AKT, promotes breast tumorigenesis by stabilizing and enhancing transcriptional activity of estrogen receptor α

Cited by 15 publications

References 43 publications

Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis

Deubiquitinase USP35 stabilizes BRPF1 to activate mevalonate (MVA) metabolism during prostate tumorigenesis

MYSM1 co-activates ERα action via histone and non-histone deubiquitination to confer antiestrogen resistance in breast cancer

Mitochondria, mitophagy, and the role of deubiquitinases as novel therapeutic targets in liver pathology

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