Hepatitis B Virus Protein X Induces Degradation of Talin-1

Klundert, Maarten van de; Biggelaar, Maartje van den; Kootstra, Neeltje A.; Zaaijer, Hans L.

doi:10.3390/v8100281

Cited by 16 publications

(13 citation statements)

References 77 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the mechanisms responsible for the development of HBV-induced HCC remain largely unknown. There has been much evidence suggesting that HBx, one of four proteins encoded by HBV genome, plays a critical role in the pathogenesis of HBV-related HCC through influencing several cellular processes including cell cycle progression [ 33 ], apoptosis [ 34 ], DNA repair [ 35 ], protein degradation [ 36 ], and signal transduction [ 16 ]. However, the underlying mechanisms of HBx-induced HCC remain obscured.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X protein-induced hepatocellular carcinoma development

et al. 2017

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Chronic hepatitis B virus (HBV) infection is a major cause for HCC. Hepatitis B virus X (HBx), one of four proteins encoded by HBV genome, plays a vital role in the pathogenesis of HBV-induced HCC. However, the molecular mechanisms of HBx-triggered HCC remain largely undetermined. Here we revealed that the expression of Brain-expressed X-linked 2 (BEX2) and Osteopontin (OPN) were elevated in liver tissues of HBV transgenic mice and human HCC specimens. Moreover, a positive correlation between BEX2 and OPN was exhibited in samples from HCC patients with HBV infection. The protein levels of BEX2 and OPN were both higher in HBV-positive HCC specimens compared to that of HBV-negative HCC specimens. HBx potentiated OPN expression through up-regulation of BEX2. Importantly, the depletion of BEX2 suppressed tumorigenic potential of HCC cells with highly expressed HBx. We demonstrated the important role of BEX2 in HCC pathogenesis, and BEX2 may be a novel therapeutic target for HCC patients with HBV infection. The newly identified HBx/BEX2/OPN signaling cassette is implicated in the pathogenesis of HBV-induced HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X protein-induced hepatocellular carcinoma development

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Several viruses encode proteins that specifically interact with the CRL4 complex (Table 1) (reviewed in Reference [38]), one of over 200 distinct CRLs in human cells (reviewed in Reference [39]). These virus-cell interactions result in degradation of critical innate immune response proteins [40,41], disruption of the cell cycle [42,43], and degradation of viral restriction factors [12][13][14] (Table 1). Identifying the critical function(s) provided by the HBx-DDB1 interaction has been difficult, in part due to the lack of convenient and authentic HBV infection models in cell culture.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B Virus HBx Protein Mediates the Degradation of Host Restriction Factors through the Cullin 4 DDB1 E3 Ubiquitin Ligase Complex

Minor

Hollinger

McNees

et al. 2020

Cells

View full text Add to dashboard Cite

The hepatitis B virus (HBV) regulatory HBx protein is required for infection, and its binding to cellular damaged DNA binding protein 1 (DDB1) is critical for this function. DDB1 is an adaptor protein for the cullin 4A Really Interesting New Gene (RING) E3 ubiquitin ligase (CRL4) complex and functions by binding cellular DDB1 cullin associated factor (DCAF) receptor proteins that recruit substrates for ubiquitination and degradation. We compared the proteins found in the CRL4 complex immunoprecipitated from uninfected versus HBV-infected hepatocytes from human liver chimeric mice for insight into mechanisms by which HBV and the cell interact within the CRL4 complex. Consistent with its role as a viral DCAF, HBx was found in the HBV CRL4 complexes. In tissue culture transfection experiments, we showed that HBx expression led to decreased levels of known restriction factor structural maintenance of chromosomes protein 6 (SMC6) and putative restriction factors stromal interaction molecule 1 (STIM1, zinc finger E-box binding homeobox 2 (ZEB2), and proteasome activator subunit 4 (PSME4). Moreover, silencing of these proteins led to increased HBV replication in the HepG2-sodium taurocholate cotransporting polypeptide (NTCP) infection model. We also identified cellular DCAF receptors in CRL4 complexes from humanized mice. Increasing amounts of HBx did not reveal competitive DCAF binding to cullin4 (CUL4)-DDB1 in plasmid-transfected cells. Our results suggest a model in which HBx benefits virus replication by directly or indirectly degrading multiple cellular restriction factors.

show abstract

“…Lactadherin has been reported to bind specifically to rotavirus and inhibits its replication [50]. Talin-1 can act as a viral restriction factor that suppresses hepatitis B virus replication [51]. Vimentin is known to be involved in virus attachment and entry [52].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of the Human Fetal Multipotent Mesenchymal Stromal Cells Secretome

et al. 2020

View full text Add to dashboard Cite

Secretome of multipotent mesenchymal stromal cells (MSCs) is actively used in biomedical applications such as alveolar bone regeneration, treatment of cardiovascular disease, and neurodegenerative disorders. Nevertheless, hMSCs have low proliferative potential and production of the industrial quantity of their secretome might be challenging. Human fetal multipotent mesenchymal stromal cells (FetMSCs) isolated from early human embryo bone marrow are easy to expand and might be a potential source for pharmaceutical substances production based on their secretome. However, the secretome of FetMSCs was not previously analyzed. Here, we describe the secretome of FetMSCs using LC-MALDI shotgun proteomics. We identified 236 proteins. Functional annotation of the identified proteins revealed their involvement in angiogenesis, ossification, regulation of apoptosis, and immune response processes, which made it promising for biomedical applications. The proteins identified in the FetMSCs secretome are involved in the same biological processes as proteins from previously described adult hMSCs secretomes. Nevertheless, many of the common hMSCs secretome components (such as VEGF, FGF, Wnt and TGF-β) have not been identified in the FetMSCs secretome.

show abstract

Hepatitis B Virus Protein X Induces Degradation of Talin-1

Cited by 16 publications

References 77 publications

Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X protein-induced hepatocellular carcinoma development

Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X protein-induced hepatocellular carcinoma development

Hepatitis B Virus HBx Protein Mediates the Degradation of Host Restriction Factors through the Cullin 4 DDB1 E3 Ubiquitin Ligase Complex

Proteomic Profiling of the Human Fetal Multipotent Mesenchymal Stromal Cells Secretome

Contact Info

Product

Resources

About