HBV X Protein Induces Degradation of UBXN7, a Novel Negative Regulator of NF-κB Signaling, to Promote HBV Replication

Yuan, Shuo; Wang, Min; Huang, Junsong; Ma, Shenglin; Liu, Yang; Ke, Yujia; Zeng, Xianhuang; Wu, Kang-Wei; Wang, Jingwen; Tian, Xuezhang; Zheng, Dandan; Yousaf, Tanzeel; Naz, Wajeeha; Sun, Junwei; Chen, Lang; Guo, Deyin; Guo, Mingxiong; Sun, Guihong

doi:10.1016/j.jcmgh.2022.09.003

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…In the NF-κB signaling pathway system, Hbx is able to degrade UBXN7, a member of the ubiquitin regulatory X proteins and a negative regulator of NF-κB. This degradation activates NF-κB signaling and autophagy and affects HBV replication [ 54 ].…”

Section: Hbx Role In Hepatocarcinogenesismentioning

confidence: 99%

“…Several recent studies further demonstrated the role of HBx in several pathways related to autophagy. In response to Toll-like receptor 4 (TLR4) stimulation, HBx is involved, the retain of the BECN1-Bcl-2 complex and the boost of the TRAF6-BECN1-VPS34 complex, thus enhancing tumor progression [53]. In the NF-κB signaling pathway system, Hbx is able to degrade UBXN7, a member of the ubiquitin regulatory X proteins and a negative regulator of NF-κB.…”

Section: Hbx and Autophagy Mechanismmentioning

confidence: 99%

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The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates

Agustiningsih,

Rasyak,

Turyadi

et al. 2024

Exploration of Targeted Anti-Tumor Therapy

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Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancers with high mortality rate. Among its various etiological factors, one of the major risk factors for HCC is a chronic infection of hepatitis B virus (HBV). HBV X protein (HBx) has been identified to play an important role in the HBV-induced HCC pathogenesis since it may interfere with several key regulators of many cellular processes. HBx localization within the cells may be beneficial to HBx multiple functions at different phases of HBV infection and associated hepatocarcinogenesis. HBx as a regulatory protein modulates cellular transcription, molecular signal transduction, cell cycle, apoptosis, autophagy, protein degradation pathways, and host genetic stability via interaction with various factors, including its association with various non-coding RNAs. A better understanding on the regulatory mechanism of HBx on various characteristics of HCC would provide an overall picture of HBV-associated HCC. This article addresses recent data on HBx role in the HBV-associated hepatocarcinogenesis.

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Section: Hbx Role In Hepatocarcinogenesismentioning

confidence: 99%

Section: Hbx and Autophagy Mechanismmentioning

confidence: 99%

The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates

Agustiningsih,

Rasyak,

Turyadi

et al. 2024

Exploration of Targeted Anti-Tumor Therapy

View full text Add to dashboard Cite

show abstract

“…3389/fmicb.2023.1322892 Frontiers in Microbiology 07 frontiersin.org IKK-B, which activates the NF-kB signaling pathway and NF-kBdependent autophagy. Targeting UBXN7 may present a therapeutic approach for HBV-related conditions (Yuan et al, 2022). HBx has also demonstrated an affinity for beta interferon promoter stimulator 1 (IPS-1), a pivotal adaptor protein for IFN-β activation.…”

Section: The Interaction Of Hbx and Ifn Signal Pathway Regulation Of ...mentioning

confidence: 99%

Role of hepatitis B virus non-structural protein HBx on HBV replication, interferon signaling, and hepatocarcinogenesis

Wang,

Song,

et al. 2023

Front. Microbiol.

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Hepatitis B, a global health concern caused by the hepatitis B virus (HBV), infects nearly 2 billion individuals worldwide, as reported by the World Health Organization (WHO). HBV, a hepatotropic DNA virus, predominantly targets and replicates within hepatocytes. Those carrying the virus are at increased risk of liver cirrhosis and hepatocellular carcinoma, resulting in nearly 900,000 fatalities annually. The HBV X protein (HBx), encoded by the virus’s open reading frame x, plays a key role in its virulence. This protein is integral to viral replication, immune modulation, and liver cancer progression. Despite its significance, the precise molecular mechanisms underlying HBx remain elusive. This review investigates the HBx protein’s roles in HBV replication, interferon signaling regulation, and hepatocellular carcinoma progression. By understanding the complex interactions between the virus and its host mediated by HBx, we aim to establish a solid foundation for future research and the development of HBx-targeted therapeutics.

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Targeted protein degradation: advances in drug discovery and clinical practice

Zhong,

Chang,

Xie

et al. 2024

Sig Transduct Target Ther

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Targeted protein degradation (TPD) represents a revolutionary therapeutic strategy in disease management, providing a stark contrast to traditional therapeutic approaches like small molecule inhibitors that primarily focus on inhibiting protein function. This advanced technology capitalizes on the cell’s intrinsic proteolytic systems, including the proteasome and lysosomal pathways, to selectively eliminate disease-causing proteins. TPD not only enhances the efficacy of treatments but also expands the scope of protein degradation applications. Despite its considerable potential, TPD faces challenges related to the properties of the drugs and their rational design. This review thoroughly explores the mechanisms and clinical advancements of TPD, from its initial conceptualization to practical implementation, with a particular focus on proteolysis-targeting chimeras and molecular glues. In addition, the review delves into emerging technologies and methodologies aimed at addressing these challenges and enhancing therapeutic efficacy. We also discuss the significant clinical trials and highlight the promising therapeutic outcomes associated with TPD drugs, illustrating their potential to transform the treatment landscape. Furthermore, the review considers the benefits of combining TPD with other therapies to enhance overall treatment effectiveness and overcome drug resistance. The future directions of TPD applications are also explored, presenting an optimistic perspective on further innovations. By offering a comprehensive overview of the current innovations and the challenges faced, this review assesses the transformative potential of TPD in revolutionizing drug development and disease management, setting the stage for a new era in medical therapy.

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HBV X Protein Induces Degradation of UBXN7, a Novel Negative Regulator of NF-κB Signaling, to Promote HBV Replication

Cited by 5 publications

References 30 publications

The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates

The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates

Role of hepatitis B virus non-structural protein HBx on HBV replication, interferon signaling, and hepatocarcinogenesis

Targeted protein degradation: advances in drug discovery and clinical practice

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