USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication

Pan, Ting; Zheng, Sifa; Wu, Liyang; Liu, Guangyan; Ma, Xiancai; Peng, Zhilin; Zhou, Mo; Liang, Liting; Liu, Bingfeng; Li, Jun; Zhang, Junsong; Zhang, Xuanhong; Huang, Ryan; Zhao, Jiacong; Li, Yonghong; Ling, Xuemei; Luo, Yong; Tang, Xiaoping; Cai, Weiping; Deng, Kai; Li, Linghua; Zhang, Hui

doi:10.7554/elife.48318

Cited by 22 publications

(18 citation statements)

References 65 publications

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“…Deubiquitinases belong to proteases, which could play important roles in modulating the stability, activity, and translocation of targeted protein by removing its ubiquitins (Xiao et al, 2016). For instance, Ubiquitin Specific Protease 49 (USP49) was previously shown to interact with apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) to rapidly remove its ubiquitin, which efficiently stabilizes A3G and augments A3G protein expression levels, and further inhibited the replication of HIV-1 (Pan et al, 2019). Meanwhile, SIRT1 has been reported to exert a protective role in myocardia injury (Fu et al, 2017), whereas our findings demonstrated that SIRT1 expression was repressed in myocardial tissue after MI/R injury, whereby its elevation reduced the extent of MI/R injury by enhancing cardiomyocyte viability and diminishing ferroptosisinduced cell death.…”

Section: Discussionmentioning

confidence: 99%

USP22 Protects Against Myocardial Ischemia–Reperfusion Injury via the SIRT1-p53/SLC7A11–Dependent Inhibition of Ferroptosis–Induced Cardiomyocyte Death

Sun

et al. 2020

Front. Physiol.

122

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Myocardial ischemia-reperfusion (MI/R) injury is characterized by iron deposition and reactive oxygen species production, which can induce ferroptosis. Ferroptosis has also been proposed to promote cardiomyocyte death. The current study sought to define the mechanism governing cardiomyocyte death in MI/R injury. An animal model of MI/R was established by ligation and perfusion of the left anterior descending coronary artery, and a cellular model of IR was constructed in cardiomyocytes. ChIP assay was then conducted to determine the interaction among USP22, SIRT1, p53, and SLC7A11. Loss-and gain-of-function assays were also conducted to determine the in vivo and in vitro roles of USP22, SIRT1, and SLC7A11. The infarct size and pathological changes of myocardial tissue were observed using TCC and hematoxylin-eosin staining, and the levels of cardiac function-and myocardial injury-related factors of rats were determined. Cardiomyocyte viability and apoptosis were evaluated in vitro, followed by detection of ferroptosis-related indicators (glutathione (GSH), reactive oxygen species, lipid peroxidation, and iron accumulation). USP22, SIRT1, and SLC7A11 expressions were found to be down-regulated, whereas p53 was highly expressed during MI/R injury. USP22, SIRT1, or SLC7A11 overexpression reduced the infarct size and ameliorated pathological conditions, cardiac function, as evidenced by reduced maximum pressure, ejection fraction, maximum pressure rate, and myocardial injury characterized by lower creatine phosphokinase and lactate dehydrogenase levels in vivo. Moreover, USP22, SIRT1, or SLC7A11 elevation contributed to enhanced cardiomyocyte viability and attenuated ferroptosis-induced cell death in vitro, accompanied by increased GSH levels, as well as decreased reactive oxygen species production, lipid peroxidation, and iron accumulation. Together, these results demonstrate that USP22 overexpression could inhibit ferroptosis-induced cardiomyocyte death to protect against MI/R injury via the SIRT1/p53/SLC7A11 association.

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Section: Discussionmentioning

confidence: 99%

USP22 Protects Against Myocardial Ischemia–Reperfusion Injury via the SIRT1-p53/SLC7A11–Dependent Inhibition of Ferroptosis–Induced Cardiomyocyte Death

Sun

et al. 2020

Front. Physiol.

122

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“…Western blot assay was performed as described previously. 59 – 61 Supernatants derived from ~2–4 plates of HEK293T (15 cm plate) or derived from eight plates of 16HBE or H1299 cells were collected for purified exosomes. Cells or purified exosomes were lysed and the concentration was measured by the Bradford method.…”

Section: Methodsmentioning

confidence: 99%

The interferon-stimulated exosomal hACE2 potently inhibits SARS-CoV-2 replication through competitively blocking the virus entry

Zhang

Huang

Xia

et al. 2021

Sig Transduct Target Ther

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Since the outbreak of coronavirus disease 2019 (COVID-19), it has become a global pandemic. The spike (S) protein of etiologic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specifically recognizes human angiotensin-converting enzyme 2 (hACE2) as its receptor, which is recently identified as an interferon (IFN)-stimulated gene. Here, we find that hACE2 exists on the surface of exosomes released by different cell types, and the expression of exosomal hACE2 is increased by IFNα/β treatment. In particular, exosomal hACE2 can specifically block the cell entry of SARS-CoV-2, subsequently inhibit the replication of SARS-CoV-2 in vitro and ex vivo. Our findings have indicated that IFN is able to upregulate a viral receptor on the exosomes which competitively block the virus entry, exhibiting a potential antiviral strategy.

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“…It is reported that USP49 is a new antiviral factor. USP49 increased A3G protein expression by removing ubiquitin and enhanced its anti-HIV-1 activity ( 35 ). Different from USP49, we discovered that USP8 is a potent and specific inhibitor of Vif.…”

Section: Discussionmentioning

confidence: 99%

Specific Deubiquitinating Enzymes Promote Host Restriction Factors Against HIV/SIV Viruses

Gao

Rui

et al. 2021

Front. Immunol.

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Hijacking host ubiquitin pathways is essential for the replication of diverse viruses. However, the role of deubiquitinating enzymes (DUBs) in the interplay between viruses and the host is poorly characterized. Here, we demonstrate that specific DUBs are potent inhibitors of viral proteins from HIVs/simian immunodeficiency viruses (SIVs) that are involved in viral evasion of host restriction factors and viral replication. In particular, we discovered that T cell-functioning ubiquitin-specific protease 8 (USP8) is a potent and specific inhibitor of HIV-1 virion infectivity factor (Vif)-mediated apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3)G (A3G) degradation. Ectopic expression of USP8 inhibited Vif-induced A3G degradation and suppressed wild-type HIV-1 infectivity even in the presence of Vif. In addition, specific DUBs repressed Vpr-, Vpu-, and Vpx-triggered host restriction factor degradation. Our study has revealed a previously unrecognized interplay between the host’s DUBs and viral replication. Enhancing the antiviral activity of DUBs therefore represents an attractive strategy against HIVs/SIVs.

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USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication

Cited by 22 publications

References 65 publications

USP22 Protects Against Myocardial Ischemia–Reperfusion Injury via the SIRT1-p53/SLC7A11–Dependent Inhibition of Ferroptosis–Induced Cardiomyocyte Death

USP22 Protects Against Myocardial Ischemia–Reperfusion Injury via the SIRT1-p53/SLC7A11–Dependent Inhibition of Ferroptosis–Induced Cardiomyocyte Death

The interferon-stimulated exosomal hACE2 potently inhibits SARS-CoV-2 replication through competitively blocking the virus entry

Specific Deubiquitinating Enzymes Promote Host Restriction Factors Against HIV/SIV Viruses

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