The membrane-associated ubiquitin ligase MARCHF8 stabilizes the human papillomavirus oncoprotein E7 by degrading CUL1 and UBE2L3 in head and neck cancer DOI Creative Commons
M. I. Khalil, Canchai Yang, Lexi Vu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 4, 2023

The human papillomavirus (HPV) oncoprotein E7 is a relatively short-lived protein required for HPV-driven cancer development and maintenance. degraded through ubiquitination mediated by cullin 1 (CUL1) the ubiquitin-conjugating enzyme E2 L3 (UBE2L3). However, proteins are maintained at high levels in most HPV-positive cells. A previous proteomics study has shown that UBE2L3 CUL1 increased knockdown of E3 ubiquitin ligase membrane-associated ring-CH-type finger 8 (MARCHF8). We have recently demonstrated HPV upregulates MARCHF8 expression keratinocytes head neck (HPV+ HNC) Here, we report stabilizes degrading components SKP1-CUL1-F-box (SCF) complex HPV+ HNC found

Language: Английский

Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain DOI Creative Commons
Changqing Yu,

Yuanzhe Bai,

Wenbo Tan

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(2)

Published: Feb. 1, 2024

Abstract Membrane‐associated RING‐CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes. Previous work showed that human MARCH8 blocked Ebola virus (EBOV) glycoprotein (GP) maturation. Our study here demonstrates MARCH1 and MARCH2 share a similar pattern in restricting EBOV GP‐pseudotyped infection. Human retain GP at the trans ‐Golgi network, reduce its cell surface display, impair virions infectivity. Furthermore, we uncover host proprotein convertase furin could interact with MARCH1/2 intracellularly. Importantly, P domain is verified be recognized by MARCH1/2/8, which critical for their blocking activities. Besides, bovine murine also proteolytic processing. Altogether, our findings confirm of different mammalian origins relatively conserved feature cleavage, provide clues subsequent MARCHs antiviral studies may facilitate development novel strategies antagonize enveloped

Language: Английский

Citations

13
Host antiviral factors hijack furin to block SARS-CoV-2, ebola virus, and HIV-1 glycoproteins cleavage DOI Creative Commons
Changqing Yu, Guosheng Wang, Qiang Liu

et al.

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(1)

Published: Jan. 2, 2023

Viral envelope glycoproteins are crucial for viral infections. In the process of enveloped viruses budding and release from producer cells, presented on membrane surface as spikes, promoting virus's next-round infection target cells. However, host cells evolve counteracting mechanisms in long-term virus-host co-evolutionary processes. For instance, cell antiviral factors could potently suppress replication by targeting their through multiple channels, including intracellular synthesis, glycosylation modification, assembly into virions, binding to receptors. Recently, a group studies discovered that some proteins specifically recognized proprotein convertase (PC) furin blocked its cleavage glycoproteins, thus impairing infectivity. Here, this review, we briefly summarize several such analyze roles reducing aiming at providing insights future studies.

Language: Английский

Citations

20
The membrane-associated ubiquitin ligase MARCHF8 stabilizes the human papillomavirus oncoprotein E7 by degrading CUL1 and UBE2L3 in head and neck cancer DOI Creative Commons
M. I. Khalil, Canchai Yang, Lexi Vu

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 16, 2024

ABSTRACT The human papillomavirus (HPV) oncoprotein E7 is a relatively short-lived protein required for HPV-driven cancer development and maintenance. degraded through ubiquitination mediated by cullin 1 (CUL1) the ubiquitin-conjugating enzyme E2 L3 (UBE2L3). However, proteins are maintained at high levels in most HPV-positive cells. A previous proteomics study has shown that UBE2L3 CUL1 increased knockdown of E3 ubiquitin ligase membrane-associated ring-CH-type finger 8 (MARCHF8). We have recently demonstrated HPV16 upregulates MARCHF8 expression keratinocytes head neck (HPV+ HNC) Here, we report stabilizes degrading components S-phase kinase-associated 1-CUL1-F-box complex HPV+ HNC found cells drastically decreases level while increasing levels. further revealed binds to ubiquitinates enhances protein. Conversely, overexpression suppresses tumor growth vivo . Our findings suggest HPV-induced prevents degradation ubiquitinating proteins. IMPORTANCE Since essential virus replication; HPV maintain HPV-infected can be efficiently ubiquitinated proteasomes host cell. Mechanistically, (UBE2L3) play an role degradation. show membrane (MARCHF8) induced E6 blocking proteasomes. knockout restores expression, decreasing inhibiting proliferation Additionally, or growth. results maintains cell inducing MARCHF8, which may critical tumorigenesis.

Language: Английский

Citations

7
Influenza Virus Host Restriction Factors: The ISGs and Non-ISGs DOI Creative Commons
Matloob Husain

Pathogens, Journal Year: 2024, Volume and Issue: 13(2), P. 127 - 127

Published: Jan. 29, 2024

Influenza virus has been one of the most prevalent and researched viruses globally. Consequently, there is ample information available about influenza lifecycle pathogenesis. However, plenty yet to be known determinants pathogenesis disease severity. exploits host factors promote each step its lifecycle. In turn, deploys antiviral or restriction that inhibit restrict at those steps. Two broad categories can exist in virus-infected cells: (1) encoded by interferon-stimulated genes (ISGs) (2) constitutively expressed are not stimulated interferons (non-ISGs). There hundreds ISGs known, many, e.g., Mx, IFITMs, TRIMs, have characterized infection different stages blocking viral entry progeny release, sequestering degrading components interfering with synthesis assembly, (3) bolstering innate defenses. Also, many non-ISGs, cyclophilins, ncRNAs, HDACs, identified similar mechanisms. This review provides an overview non-ISGs how escapes imposed them aims improve our understanding mechanisms virus.

Language: Английский

Citations

7
The emerging roles of MARCH8 in viral infections: A double-edged Sword DOI Creative Commons
Changqing Yu, Qiang Liu, Zhuo Zhao

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(9), P. e1011619 - e1011619

Published: Sept. 14, 2023

The host cell membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, regulates intracellular turnover many transmembrane proteins and shows potent antiviral activities. Generally, 2 modes are performed by MARCH8. On one hand, MARCH8 catalyzes viral envelope glycoproteins (VEGs) ubiquitination thus leads to their degradation, which is cytoplasmic tail (CT)-dependent (CTD) mode. other traps VEGs at some compartments (such as trans-Golgi network, TGN) but without inducing tail-independent (CTI) mode, hijacks furin, cellular proprotein convertase, block cleavage. In addition, C-terminal tyrosine-based motif (TBM) 222YxxL225 also plays key role in its CTI effects. contrast potency, occasionally hijacked viruses bacteria enhance invasion, indicating duplex pathogenic infections. This review summarizes MARCH8's roles how evade restriction, shedding light on novel therapeutic avenues.

Language: Английский

Citations

12
Regulation of viral replication by host restriction factors DOI Creative Commons
Ying Lin, Yun Zhu, Ling Jing

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 23, 2025

Viral infectious diseases, caused by numerous viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), enterovirus (EV), human immunodeficiency (HIV), hepatitis B (HBV), and papillomavirus (HPV), pose a continuous threat to global health. As obligate parasites, rely on host cells replicate, have developed defense mechanisms counteract viral infection. Host restriction factors (HRFs) are critical components of the early antiviral response. These cellular proteins inhibit replication spread impeding essential steps in life cycle, such as entry, genome transcription replication, protein translation, particle assembly, release. This review summarizes current understanding how with primary focus their diverse against range viruses, SARS-CoV-2, virus, enteroviruses, papillomavirus. In addition, we highlight crucial role these shaping host-virus interactions discuss potential targets for drug development.

Language: Английский

Citations

0
MARCH8 ubiquitinates and degrades CEMIP to induce colorectal cancer cell ferroptosis through inactivating PI3K/AKT pathway DOI
Lintao Liu, Cheng Zhang, Bo Yang

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155909 - 155909

Published: March 11, 2025

Language: Английский

Citations

0
MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis DOI Creative Commons

Daoyuan Tu,

Rui Peng, Shengjie Jin

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 16, 2025

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors digestive system, and its prevalence currently increasing. The current study aims to elucidate mechanism by which membrane-associated RING-CH8 (MARCH8) impedes progression HCC. MARCH8 was identified as a distinct prognostic marker for recurrence-free survival (RFS) overall (OS) in patients with This shows that hinders lipid deposition suppressing expression key enzymes de novo synthesis fatty acids (FAs) via RNA sequencing, untargeted metabolomics, series vivo vitro experiments. Further experimental validation demonstrated novel E3 ligase sterol regulatory element binding protein 1 (SREBP1). And, it primarily promoted degradation SREBP1, thereby involved FAs. In conclusion, this has "switch" can be targeted prevent FA HCC cells. finding may have substantial implications discovering innovative therapeutic strategies

Language: Английский

Citations

0
MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network DOI

Cui-Hong Rao,

Rui Huang,

Yuan-Zhe Bai

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 274, P. 133463 - 133463

Published: Aug. 1, 2024

Language: Английский

Citations

3
Mouse Mx1 Inhibits Herpes Simplex Virus Type 1 Genomic Replication and Late Gene ExpressionIn Vitroand Prevents Lesion Formation in the Mouse Zosteriform Model DOI Open Access
Melkamu B. Tessema, Rubaiyea Farrukee, Christopher E. Andoniou

et al.

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(12)

Published: May 31, 2022

While a number of studies have demonstrated that human Mx proteins can inhibit particular herpesviruses in vitro , we are the first to report antiviral activity mouse Mx1 (mMx1) against alphaherpesviruses both and vivo . We demonstrate overexpressed mMx1 endogenous potently restrict HSV-1 growth mMx1-mediated inhibition was not associated with virus entry and/or import viral genome into nucleus, but rather genomic replication as well subsequent late gene expression.

Language: Английский

Citations

9