Versatility of USP18 in physiology and pathophysiology

Dziamałek-Macioszczyk, Paulina; Harazny, Joanna; Stompór, Tomasz

doi:10.18388/abp.2019_2844

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…Ubiquitin‐specific peptidase 18 (USP18) is considered a critical multifunctional deubiquitinase that moderates the stability of key proteins to contribute to the carcinogenesis process. [ 43 , 44 ] Recently, PD‐1/PD‐L1‐targeting immune checkpoint inhibitors (ICIs) have been proven to be promising treatment modalities in bladder cancer. [ 45 , 46 ] Our study demonstrated that USP18 downregulation caused by BCCE4 [A] could decrease the protein stability of PD‐L1, attenuate the PD‐L1/PD‐1 interaction and sensitize bladder cancer cells to T‐cell‐mediated killing.…”

Section: Discussionmentioning

confidence: 99%

LncRNA BCCE4 Genetically Enhances the PD‐L1/PD‐1 Interaction in Smoking‐Related Bladder Cancer by Modulating miR‐328‐3p‐USP18 Signaling

Zheng,

Gao,

Mao

et al. 2023

Advanced Science

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Identification of cancer‐associated variants, especially those in functional regions of long noncoding RNAs (lncRNAs), has become an essential task in tumor etiology. However, the genetic function of lncRNA variants involved in bladder cancer susceptibility remains poorly understood. Herein, it is identified that the rs62483508 G > A variant in microRNA response elements (MREs) of lncRNA Bladder cancer Cell Cytoplasm‐Enriched abundant transcript 4 (BCCE4) is significantly associated with decreased bladder cancer risk (odds ratio = 0.84, P = 7.33 × 10−8) in the Chinese population (3603 cases and 4986 controls) but not in the European population. The protective genetic effect of the rs62483508 A allele is found in smokers or cigarette smoke‐related carcinogen 4‐aminobiphenyl (4‐ABP) exposure. Subsequent biological experiments reveal that the A allele of rs62483508 disrupts the binding affinity of miR‐328‐3p to facilitate USP18 from miRNA‐mediated degradation and thus specifically attenuates the downstream PD‐L1/PD‐1 interaction. LncRNA BCCE4 is also enriched in exosomes from bladder cancer plasma, tissues, and cells. This comprehensive study clarifies the genetic mechanism of lncRNA BCCE4 in bladder cancer susceptibility and its role in the regulation of the immune response in tumorigenesis. The findings provide a valuable predictor of bladder cancer risk that can facilitate diagnosis and prevention.

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Section: Discussionmentioning

confidence: 99%

LncRNA BCCE4 Genetically Enhances the PD‐L1/PD‐1 Interaction in Smoking‐Related Bladder Cancer by Modulating miR‐328‐3p‐USP18 Signaling

Zheng,

Gao,

Mao

et al. 2023

Advanced Science

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“…This process can be reversed by deubiquitinase enzymes, which are central to its regulation. Moreover, ubiquitin-like proteins also participate in post-translational modifications via mechanisms similar to ubiquitination (9,10). Ubiquitin-specific peptidase 18 (USP18), also known as ISG43, UBP43, and PTORCH2, is a member of the USP family that deubiquitinates proteins.…”

Section: Generalities Of Ubiquitin Specific Peptidase 18 (Usp18)mentioning

confidence: 99%

Ubiquitin-Specific Peptidase 18: A Multifaceted Protein Participating in Breast Cancer

Tecalco-Cruz¹,

Ramírez-Jarquín²,

Zepeda–Cervantes³

et al. 2022

Breast Cancer

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“…Ubiquitin-specific peptidase 18 (USP18) is a multifunctional protein 20 . Originally, USP18 is identified as the deISGlase and removes interferon-stimulated gene 15 (ISG15) from the substrate proteins 21 .…”

Section: Introductionmentioning

confidence: 99%

USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS

et al. 2021

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Activation of MAVS, an adaptor molecule in Rig-I-like receptor (RLR) signaling, is indispensable for antiviral immunity, yet the molecular mechanisms modulating MAVS activation are not completely understood. Ubiquitination has a central function in regulating the activity of MAVS. Here, we demonstrate that a mitochondria-localized deubiquitinase USP18 specifically interacts with MAVS, promotes K63-linked polyubiquitination and subsequent aggregation of MAVS. USP18 upregulates the expression and production of type I interferon following infection with Sendai virus (SeV) or Encephalomyocarditis virus (EMCV). Mice with a deficiency of USP18 are more susceptible to RNA virus infection. USP18 functions as a scaffold protein to facilitate the re-localization of TRIM31 and enhances the interaction between TRIM31 and MAVS in mitochondria. Our results indicate that USP18 functions as a post-translational modulator of MAVS-mediated antiviral signaling.

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Versatility of USP18 in physiology and pathophysiology

Cited by 7 publications

References 28 publications

LncRNA BCCE4 Genetically Enhances the PD‐L1/PD‐1 Interaction in Smoking‐Related Bladder Cancer by Modulating miR‐328‐3p‐USP18 Signaling

LncRNA BCCE4 Genetically Enhances the PD‐L1/PD‐1 Interaction in Smoking‐Related Bladder Cancer by Modulating miR‐328‐3p‐USP18 Signaling

Ubiquitin-Specific Peptidase 18: A Multifaceted Protein Participating in Breast Cancer

USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS

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