MARCHF1

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase MARCHF1, FLJ20668, MARCH-I

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Introduction

E3 ubiquitin-protein ligase that mediates ubiquitination of TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. By constitutively ubiquitinating MHC class II proteins in immature dendritic cells, down-regulates their cell surface localization thus sequestering them in the intracellular endosomal system.

100 Clinical Results associated with MARCHF1

100 Translational Medicine associated with MARCHF1

0 Patents (Medical) associated with MARCHF1

114

Literatures (Medical) associated with MARCHF1

01 Apr 2025·Journal of Medical Virology

SARS‐CoV‐2 Membrane Protein Induces MARCHF1/GPX4‐Mediated Ferroptosis by Promoting Lipid Accumulation

Article

Author: Yuan, Shuofeng ; Wang, Xin‐Tao ; Qiu, Ye ; Sun, Pei ; Ge, Xing‐Yi ; Liu, Qian

ABSTRACTThe membrane protein (M), a key structural protein of SARS‐CoV‐2 that regulates virus assembly and morphogenesis, is involved in the pathological processes of multiple organ damage and metabolic disorders. This study aims to elucidate the mechanisms of M‐mediated host ferroptosis and lipid accumulation during SARS‐CoV‐2 infection. Here, we detected that M protein enhances cellular sensitivity to ferroptosis. Additionally, we uncovered the pivotal role of perilipin‐2 and sterol regulatory element‐binding protein 1 in M‐induced lipid accumulation. Xanthohumol, a cost‐effective and orally available diacylglycerol acyltransferase inhibitor, alleviated triglyceride and total cholesterol accumulation, thereby counteracting the M‐induced ferroptosis. Furthermore, we identified that the mitochondrial import inner membrane translocase subunit TIM23 and the mitochondrial import receptor subunit TOM20 homolog contribute to M‐induced mitochondrial dysfunction. Notably, inhibiting lipid synthesis effectively reduced mitochondrial reactive oxygen species and transmembrane potential, indicating a cross‐talk between lipid and ferro metabolic pathways. Mechanistically, glutathione peroxidase 4 (GPX4) interacts with SARS‐CoV‐2 M, leading to its subsequent degradation by the Membrane Associated Ring‐CH‐Type Finger 1 (MARCHF1) ubiquitin ligase. M‐GPX4 interaction occurs at the R72 residue, which may represent a potential therapeutic target against SARS‐CoV‐2 infection. M modulates lipid accumulation and further impairs mitochondrial functions, ultimately resulting in ferroptosis through MARCHF1‐GPX4 axis. Disrupting host‐virus interactions along this pathway may provide a therapeutic strategy for SARS‐CoV‐2 infection.

01 Mar 2025·Cancer Communications

Radiotherapy‐resistant prostate cancer cells escape immune checkpoint blockade through the senescence‐related ataxia telangiectasia and Rad3‐related protein

Article

Author: Li, Hang ; Li, Jiaze ; Wang, Sen ; Zhao, Yu ; Wen, Simeng ; Huang, Ting ; Chen, Jiajia ; Shao, Chenyi ; Zhang, Yingyi ; Fan, Saijun

AbstractBackgroundThe majority of patients with prostate cancer (PCa) exhibit intrinsic resistance to immune checkpoint blockade (ICB) following radiotherapy (RT). This resistance is generally attributed to the limited antigen presentation of heterogeneous cells within tumors. Here, we aimed to isolate and characterize these diverse subgroups of tumor post‐RT to understand the molecular mechanisms of their resistance to ICB.MethodsSingle‐cell RNA‐sequencing (scRNA‐seq) was used to profile senescent cancer cell clusters induced by RT in LNCaP cells. The expression and phosphorylation levels of ataxia telangiectasia and Rad3‐related protein (ATR) were assessed by immunohistochemistry in clinical samples from patients with or without RT. Co‐immunoprecipitation, mutagenesis, and Western blotting were used to measure the interactions between proteins. Xenograft experiments were performed to assess the tumor immune response in the mice.ResultsWe identified a subset of PCa cells that exhibited resistance to RT, characterized by a reduced antigen presentation capability, which enhanced their ability to evade immune detection and resist cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) blockade. scRNA‐seq revealed that the senescent state was a transient phase of PCa cells post‐RT, particularly in CTLA‐4 blockade treatment‐resistant cells. This state was marked by increased cytosolic ATR level. Cytosolic ATR phosphorylated CD86 in its cytosolic domain and enhanced the interaction between CD86 and its E3 ligase MARCH1 through electrostatic attraction. Depletion or inhibition of Atr increased the sensitivity to immune attack and improved responses to anti‐Ctla‐4 antibody treatment in a mouse model.ConclusionsOur findings indicate that the activation of cytosolic ATR, which is associated with cellular senescence, impedes the effectiveness of combined RT and ICB treatments. This discovery may provide valuable insights for improving the efficacy of combined RT and ICB therapies in PCa.

01 Feb 2025·Cell Biology International

MARCHF1 promotes breast cancer through accelerating REST ubiquitylation and following TFAM transcription

Article

Author: Gao, Zhenming ; Li, Jutao

AbstractBreast cancer has become the leading cause of death in women. Membrane associated ring‐CH‐type finger 1 (MARCHF1) is associated with the development of various types of cancer, but the exact role of MARCHF1 in breast cancer remains unclear. In our study, the higher MARCHF1 expression was observed in tumor samples of patients with breast cancer and then the role of MARCHF1 in breast cancer was further evaluated. Overexpression of MARCHF1 contributed to proliferation of cancer cells and inhibition of oxidative stress. Knockdown of MARCHF1 reduced breast cancer cell proliferation, increased mitochondrial dysfunction induced by oxidative stress, eventually aggravating cell death. In vivo, MARCHF1 promoted the tumor growth and oppositely, MARCHF1 silencing suppressed the tumor development. Moreover, MARCHF1 interacted with repressor Element‐1 silencing transcription factor (REST) and facilitated its ubiquitylation and degradation. Subsequently, REST negatively regulated the transcription of mitochondrial transcription factor A (TFAM). The subcutaneous tumor formation assay in nude mice also supported these conclusions. In details, knockdown of MARCHF1 upregulated the protein expression of REST and downregulated the mRNA level of TFAM. On the contrary, MARCHF1 overexpression exhibited opposite effects. Thus, MARCHF1 is conducive to the progression of breast cancer via promoting the ubiquitylation and degradation of RSET and then the transcription of TFAM. Downregulating MARCHF1 could provide a novel direction for treating breast cancer.

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