When the chains do not break: the role of USP10 in physiology and pathology

Bhattacharya, Udayan; Neizer‐Ashun, Fiifi; Mukherjee, Priyabrata; Bhattacharya, Resham

doi:10.1038/s41419-020-03246-7

Cited by 52 publications

(34 citation statements)

References 103 publications

(134 reference statements)

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“…USP10 is an important member of the ubiquitin-specific protease family, which has been found to be widely expressed in both cytoplasm and nucleus of almost all cells. As a deubiquitinating enzyme, USP10 could reverse the ubiquitination of substrates through removing ubiquitin (Ub) molecules from the C-terminal of Ub-conjugated target proteins and maintain intracellular protein homeostasis by recycling Ub [ 35 ]. Accumulating evidence demonstrated that USP10 play crucial roles as a tumor-promoter or tumor-suppressor in the tumorigenesis and development of various cancers.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10

et al. 2022

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Background Hypoxia has long been considered as a hallmark of solid tumors and is closely associated with tumor progression. Circular RNAs (circRNAs) have been identified as a critical modulator in various cancers. However, the connections between hypoxia and circRNAs are largely unknown. Methods Here, we investigated the expression profile of circRNAs in breast cancer (BC) MCF-7 cells under hypoxia and normoxia using microarray. We identified a novel hypoxia-responsive circRNA named circWSB1, whose expression pattern, potential diagnostic value and prognostic significance were assessed by qRT-PCR and in situ hybridization. Loss- and gain-of-function investigations in vivo and in vitro were performed to determine the biological functions of circWSB1. Mechanistically, chromatin immunoprecipitation and dual luciferase reporter assays were carried out to analyze the biogenesis of circWSB1. Furthermore, biotin-labeled RNA pull-down, mass spectrometry, RNA immunoprecipitation, fluorescent in situ hybridization, RNA electrophoretic mobility shift, deletion-mapping, co-immunoprecipitation assays and rescue experiments were applied to investigate the interaction between circWSB1 and Ubiquitin-specific peptidase 10 (USP10) as well as the relationship between USP10 and p53. Results We found that the expression of circWSB1 was significantly upregulated in BC tissues and correlated with poor clinical outcomes, which might serve as an independent prognostic factor for BC patients. Ectopic expression of circWSB1 promoted the proliferation of BC cell in vitro and in vivo. Mechanistically, circWSB1 was transcriptionally upregulated by HIF1α in response to hypoxia and could competitively bind to deubiquitinase USP10 to prevent the access of p53 to USP10 in BC cells, leading to degradation of p53 and tumor progression of BC. Conclusions Taken together, our findings disclose a novel mechanism that hypoxia-inducible circWSB1 could interact with USP10 to attenuate USP10 mediated p53 stabilization and promote the progression of BC, providing an alternative prognostic biomarker and therapeutic target for BC.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10

et al. 2022

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“…Subsequently, it deubiquitinates AMPK and facilitates the further activation of AMPK, forming a feedforward loop ( Hardie, 2011 ; Hornbeck et al, 2015 ). The phosphorylated Ser76 site lies in a predicted unstructured region external to the catalytic UCH domain of USP10 ( Bhattacharya et al, 2020 ). Phosphorylation may promote the activity of USP10 by inducing conformational changes in USP10 or affecting the recognition and binding of USP10 to Ub substrates.…”

Section: Ptms Can Regulate the Specificity And Activity Of Dubsmentioning

confidence: 99%

Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code

Wang

2021

Front. Pharmacol.

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Post-translational modifications such as ubiquitination play important regulatory roles in several biological processes in eukaryotes. This process could be reversed by deubiquitinating enzymes (DUBs), which remove conjugated ubiquitin molecules from target substrates. Owing to their role as essential enzymes in regulating all ubiquitin-related processes, the abundance, localization, and catalytic activity of DUBs are tightly regulated. Dysregulation of DUBs can cause dramatic physiological consequences and a variety of disorders such as cancer, and neurodegenerative and inflammatory diseases. Multiple factors, such as transcription and translation of associated genes, and the presence of accessory domains, binding proteins, and inhibitors have been implicated in several aspects of DUB regulation. Beyond this level of regulation, emerging studies show that the function of DUBs can be regulated by a variety of post-translational modifications, which significantly affect the abundance, localization, and catalytic activity of DUBs. The most extensively studied post-translational modification of DUBs is phosphorylation. Besides phosphorylation, ubiquitination, SUMOylation, acetylation, oxidation, and hydroxylation are also reported in DUBs. In this review, we summarize the current knowledge on the regulatory effects of post-translational modifications of DUBs.

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“…Moreover, Metformin, a noteworthy substance for its pharmaceutical properties, constitutes an autophagy activator [88], such as in the case of pulmonary adenocarcinoma, which undergoes apoptosis through tumor-necrosis-factor (TNF-related-Apoptosis-Inducing-Ligand (TRAIL)) [89]. For breast malignancy, in the absence of mutant BRCA1 gene, metformin can be included in therapeutic schemes with spautin-1, which constitutes an autophagy suppressor, resulting in an altered mitochondrial functional state and inducing a notable reduction incancer cell survival and progression [88,90].…”

Section: Autophagy Enhancer Agentsmentioning

confidence: 99%

The Implication of Autophagy in Gastric Cancer Progression

Koustas

Trifylli

Sarantis

et al. 2021

Life

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Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis, and strategies for clinical management. However, many gastric tumors appear to be resistant to current chemotherapeutic agents. Moreover, a significant number of gastric cancer patients, with a lack of optimal treatment strategies, have reduced survival. In recent years, multiple research data have highlighted the importance of autophagy, an essential catabolic process of cytoplasmic component digestion, in cancer. The role of autophagy as a tumor suppressor or tumor promoter mechanism remains controversial. The multistep nature of the autophagy process offers a wide array of targetable points for designing novel chemotherapeutic strategies. The purpose of this review is to summarize the current knowledge regarding the interplay between gastric cancer development and the autophagy process and decipher the role of autophagy in this kind of cancer. A plethora of different agents that direct or indirect target autophagy may be a novel therapeutic approach for gastric cancer patients.

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When the chains do not break: the role of USP10 in physiology and pathology

Cited by 52 publications

References 103 publications

Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10

Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10

Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code

The Implication of Autophagy in Gastric Cancer Progression

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