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Showing MARCHF1 — MARCH1 is a alias.

MARCHF1

E3 ubiquitin-protein ligase MARCHF1 · UniProt Q8TCQ1

Length
289 aa
Mass
32.3 kDa
Annotated
2026-06-10
72 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MARCHF1 (MARCH1) is a membrane-anchored RING-CH E3 ubiquitin ligase that serves as a central rheostat of antigen presentation by constitutively ubiquitinating the cytoplasmic tails of MHC class II and the costimulatory molecule CD86 in antigen-presenting cells, routing these molecules to lysosomes and limiting their surface display (PMID:18305173, PMID:18389477, PMID:35492398). By targeting newly synthesized peptide-MHC-II for degradation and preventing its recycling from the cell surface, MARCH1 keeps resting APCs in a low-presentation state; acute activation signals such as LPS rapidly terminate MARCH1 expression, stabilizing surface pMHC-II for CD4 T cell engagement (PMID:26240324, PMID:40397676). This ubiquitin-dependent turnover — rather than steady-state surface MHC-II levels per se — is required for conventional DC fitness, thymic regulatory T cell generation, TH2 development, lipid raft/tetraspanin web homeostasis, and indirectly for MHC class I cross-presentation (PMID:19917682, PMID:23712430, PMID:29371232, PMID:34652961, PMID:30001419). MARCH1 substrate recognition is encoded in the substrate transmembrane domain, exemplified by its requirement for proline-254 in the CD86 TM core (PMID:34157285). The ligase is held in check by multiple layers of regulation: it is induced by IL-10 in monocytes and macrophages (PMID:18389477, PMID:26408197), its substrate engagement is blocked by the transmembrane domain of CD83 (PMID:21220452, PMID:40397676) and competed by Tollip (PMID:24600555), and the protein itself is extremely short-lived (~500 molecules/cell, half-life <30 min) and is turned over via lysosomal cysteine proteases and through Ube2D1-dependent lysine-independent ubiquitination (PMID:19880452, PMID:29414787, PMID:40397676). Beyond immunity, MARCH1 ubiquitinates a broad set of membrane and intracellular targets including the insulin receptor to set basal insulin sensitivity (PMID:27577745), GPX4 to promote ferroptosis (PMID:37802009), and TBK1 via K63-linked chains to suppress mTOR signaling (PMID:39061024), and it contributes to antiviral restriction of influenza and Ebola glycoprotein trafficking (PMID:36423158, PMID:38299743).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2008 High

    Established MARCH1 as the E3 ligase that ubiquitinates MHC class II and drives its surface internalization, defining a molecular basis for maturation-controlled antigen presentation.

    Evidence Ubiquitination assays, Co-IP, and siRNA knockdown in primary human monocyte-derived DCs and IL-10-treated monocytes with surface flow cytometry

    PMID:18305173 PMID:18389477

    Open questions at the time
    • Substrate ubiquitin acceptor sites not yet mapped in these studies
    • Whether CD86 is a co-substrate not addressed
  2. 2009 High

    Showed in vivo that MHC-II ubiquitination specifically — not MARCH1 itself broadly — underlies DC function, using ubiquitination-site knockin mice that phenocopy the knockout.

    Evidence MARCH1 knockout and non-ubiquitinatable MHC-II knockin mice with in vivo antigen presentation and cytokine readouts; half-life and domain mutagenesis

    PMID:19880452 PMID:19917682

    Open questions at the time
    • Mechanism linking MHC-II accumulation to impaired antigen presentation unresolved
    • C-terminal VQNC motif role in catalysis not structurally defined
  3. 2011 High

    Defined CD83 transmembrane domain as a physiological brake that blocks MARCH1 association with MHC-II, explaining how maturation signals protect surface MHC-II and CD86.

    Evidence ENU-induced CD83 TM-domain mutant mice with IL-10 stimulation and flow cytometry

    PMID:21220452

    Open questions at the time
    • Structural basis of CD83-MARCH1 TM interference not defined
    • Whether CD83 acts as competitive decoy substrate untested
  4. 2013 High

    Connected MARCH1-dependent MHC-II turnover to immune tolerance by showing it is required for thymic Treg generation, and identified Tollip as a competing regulator.

    Evidence MARCH1 KO and ubiquitination knockin mice in Treg assays; Tollip knockdown/Co-IP in HLA-DR cells

    PMID:23712430 PMID:24600555

    Open questions at the time
    • How ubiquitin turnover translates to Treg-inducing DC signals unclear
    • Tollip mechanism (single-lab) lacks reciprocal validation
  5. 2015 High

    Resolved the trafficking logic — MARCH1 degrades newly synthesized pMHC-II and blocks its surface recycling — and showed IL-10 induction of MARCH1 is cell-type specific (macrophages, not DCs).

    Evidence MHC-II ubiquitination mutant mice with recycling and lysosomal targeting assays; cell-type-specific KO comparison with IL-10 stimulation

    PMID:26240324 PMID:26408197

    Open questions at the time
    • Sorting machinery routing ubiquitinated pMHC-II to lysosomes not fully identified
    • Transcriptional basis of cell-type-specific IL-10 responsiveness unresolved
  6. 2016 High

    Extended MARCH1 beyond immunity by identifying the insulin receptor as a basal-state substrate that sets metabolic insulin sensitivity, distinguishing MARCH1 from stimulus-dependent INSR ligases.

    Evidence RNAi screen, March1 KO and overexpression mice, INSR ubiquitination and insulin clamp studies

    PMID:27577745

    Open questions at the time
    • INSR ubiquitination site not mapped
    • Tissue-specific contribution to systemic metabolism not fully partitioned
  7. 2018 High

    Refined the self-regulation and substrate-scope picture: MARCH1 is turned over by lysine-independent, Ube2D1-dependent ubiquitination (not autoubiquitination), and unbiased proteomics confirmed CD86 and MHC-II as its only unequivocal in vivo membrane substrates in hematopoietic cells.

    Evidence Lysine-less and catalytic mutants with Ube2D1 knockdown; plasma membrane proteomics in MARCH1 and MARCH8 KO mice; double-KO MHC-I rescue; APC-specific promoter reporters

    PMID:29378848 PMID:29414787 PMID:30001419 PMID:35492398

    Open questions at the time
    • Earlier autoubiquitination model (idx 5) is contradicted — chain dependence on Ube2D1 vs MARCH1 activity needs reconciliation
    • Proteomics may miss low-abundance or non-membrane substrates later reported
  8. 2021 High

    Defined the molecular grammar of substrate recognition (CD86 TM proline-254) and broadened immune function to TH2 development and DC functional programming via MHC-II/CD86 clearance.

    Evidence Deep mutational scanning of CD86 TM; MHC-II/CD86 ubiquitin-site knockin mice in TH2 assays; scRNA-seq of ubiquitination-deficient DCs

    PMID:33318291 PMID:34157285 PMID:34652961

    Open questions at the time
    • No structure of MARCH1-substrate TM complex
    • How surface molecule clearance tunes TCR signaling strength mechanistically unresolved
  9. 2024 High

    Established quantitatively that endogenous MARCH1 is present at extremely low copy number with rapid activation-induced termination, and expanded the non-immune substrate repertoire to TBK1 (K63-linked, suppressing mTOR).

    Evidence Endogenous V5 knock-in with quantitative flow cytometry and pulse-chase; Co-IP and denatured ubiquitination assays for TBK1 with mTOR/STING/TBK1 inhibitor rescue

    PMID:39061024 PMID:40397676

    Open questions at the time
    • TBK1 finding (single-lab, Medium) lacks independent confirmation
    • Chain-type switching (K48 for MHC-II vs K63 for TBK1) determinants unknown
  10. 2025 Medium

    Reported a wave of context-specific substrates (GPX4, PCSK9, SULF1, MYCT1, REST, GABAB receptor, SLC25A17, KLF15) linking MARCH1 to ferroptosis, neuronal death, and tumor biology.

    Evidence Co-IP and ubiquitination/degradation assays with knockdown/overexpression and rescue across cancer, ischemia, and infection models

    PMID:37802009 PMID:39115562 PMID:39428668 PMID:39779794 PMID:40186530 PMID:40533483 PMID:41550717 PMID:41758657

    Open questions at the time
    • Each substrate rests on single-lab Co-IP without reciprocal/structural validation
    • Most were not detected in the unbiased in vivo proteomic screen (idx 18), raising context-dependence questions
    • Direct vs indirect ubiquitination not always disambiguated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single low-abundance, short-lived membrane ligase achieves such broad and context-specific substrate selectivity — and how chain-type and subcellular routing are determined — remains unresolved.
  • No structural model of MARCH1 with any substrate
  • Determinants selecting K48 vs K63 linkage across substrates unknown
  • Reconciliation of restricted in vivo proteomic substrate set with many reported disease-context substrates pending

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7 GO:0140096 catalytic activity, acting on a protein 5 GO:0016874 ligase activity 4
Localization
GO:0005886 plasma membrane 4 GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-392499 Metabolism of proteins 6 R-HSA-1430728 Metabolism 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CD74CD83CD86GPX4INSRTBK1TOLLIPUBE2D1

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 MARCH1 (MARCH-I) is a RING-CH E3 ubiquitin ligase that promotes ubiquitination of the HLA-DR beta-chain in human monocyte-derived dendritic cells, driving surface internalization of mature HLA-DR complexes and reducing their stability and surface levels. Maturation-dependent down-regulation of MARCH1 upon LPS stimulation is a key event in MHC class II up-regulation at the DC surface. Ubiquitination assays, siRNA knockdown in primary human monocyte-derived DCs, flow cytometry for surface HLA-DR levels, LPS maturation experiments Proceedings of the National Academy of Sciences of the United States of America High 18305173
2008 MARCH1 is induced by IL-10 in human primary monocytes and mediates intracellular sequestration of MHC class II by ubiquitinating MHC-II molecules. Direct interaction between MHC-II and MARCH1 was demonstrated by co-immunoprecipitation. siRNA-mediated knockdown of MARCH1 reverses IL-10-induced MHC-II downregulation in primary monocytes. Co-immunoprecipitation, siRNA knockdown, flow cytometry, detection of mono- and poly-ubiquitinated MHC-II in IL-10-treated monocytes European journal of immunology High 18389477
2009 MARCH1 protein has a very short half-life (<30 min) in primary dendritic cells and APC cell lines, with degradation occurring partly in lysosomes via cysteine proteases. Mutational analysis defined discrete N-terminal endosomal sorting motifs and a C-terminal domain required for proper localization, functional interaction with substrates, and protein destabilization. Mutation of C-terminal tyrosine-based sorting signals reduced incorporation into exosomes. A C-terminal 221VQNC224 motif affects the spatial organization of the two cytoplasmic tails and MARCH1 activity. Pulse-chase half-life assays, lysosomal inhibitor treatment, cysteine protease inhibitor treatment, domain deletion/point mutagenesis, fusion reporter constructs, flow cytometry Journal of immunology (Baltimore, Md. : 1950) High 19880452
2009 MARCH-I-mediated MHC II ubiquitination is necessary for the maintenance of conventional dendritic cell function in vivo. MARCH-I-deficient cDCs accumulate MHC II and B7-2 but exhibit impaired antigen-presenting ability and reduced cytokine production. Knockin mice carrying MHC II unable to be ubiquitinated phenocopy MARCH-I knockout, demonstrating the functional relevance is through MHC II ubiquitination specifically. MARCH-I knockout mice, MHC II ubiquitination knockin mice, in vivo antigen presentation assays, cytokine measurement Journal of immunology (Baltimore, Md. : 1950) High 19917682
2011 The transmembrane domain of CD83 blocks MARCH1 association with MHC class II, thereby preventing IL-10-driven, MARCH1-dependent ubiquitination and degradation of MHC class II and CD86 in dendritic cells. An ENU-induced mutation eliminating the CD83 TM region abolishes this protective effect. ENU-induced TM-domain mutant mice, flow cytometry for MHC II and CD86, IL-10 stimulation assays, genetic epistasis The Journal of experimental medicine High 21220452
2012 MARCH1 is itself ubiquitinated via K48-linked polyubiquitin chains. A lysine-less N- and C-terminal mutant has reduced ubiquitination and prolonged half-life. An inactive catalytic mutant (M1WI) also shows reduced ubiquitination, consistent with autoubiquitination. MARCH1 homodimerizes and forms heterodimers with other MARCH family members; co-expression of wild-type MARCH1 decreases levels of the inactive M1WI mutant via transubiquitination. Co-immunoprecipitation, FRET/energy transfer, polyubiquitin chain-specific antibodies, site-directed mutagenesis, pulse-chase half-life, transfection in human cell lines Journal of immunology (Baltimore, Md. : 1950) Medium 22508929
2012 MARCH1 contains N-terminal endosomal sorting motifs and a functional C-terminal 221VQNC224 motif (also found in parkin) that affects the spatial organization of its cytoplasmic tails and E3 ligase activity. Mutation of C-terminal tyrosine-based sorting signals reduces MARCH1 incorporation into exosomes. Site-directed mutagenesis, type I/II transmembrane reporter fusions, exosome fractionation, functional substrate downregulation assays Journal of cell science Medium 23264739
2013 Tollip reduces MARCH1 protein levels and competes with MARCH1 for binding to MHC II molecules. Knockdown of Tollip in HLA-DR-expressing cells increases HLA-DR surface expression and reduces CLIP-associated MHC II. Truncation of HLA-DR cytoplasmic tails abrogates Tollip's effect on MHC II expression. Tollip knockdown (siRNA), overexpression, co-immunoprecipitation, flow cytometry, reporter cell lines Results in immunology Medium 24600555
2013 MARCH1-mediated MHCII ubiquitination in dendritic cells is required for proper production of thymus-derived regulatory T cells (Treg) in vivo. DCs deficient in MARCH1 or carrying non-ubiquitinatable MHCII both fail to generate antigen-specific Treg cells despite increased surface MHCII, demonstrating that ubiquitin-dependent MHCII turnover, not MHCII surface levels per se, is critical. MARCH1 knockout mice, MHCII ubiquitination knockin mice, in vivo and in vitro Treg generation assays The Journal of experimental medicine High 23712430
2015 IL-10 stimulates expression of MARCH-I in activated macrophages (but not dendritic cells), thereby down-regulating MHC-II, CD86, and antigen presentation to CD4 T cells in a MARCH-I-dependent manner. In contrast, IL-10-mediated suppression of DC antigen presentation is MARCH-I-independent. IL-10 stimulation of macrophages vs. DCs, MARCH-I KO macrophages and DCs, flow cytometry, antigen-presentation assays The Journal of biological chemistry High 26408197
2015 March-I ubiquitination promotes degradation of newly synthesized pMHC-II and prevents pMHC-II recycling from the DC surface, routing internalized pMHC-II to lysosomes. Acute DC or B cell activation terminates March-I expression, which results in efficient pMHC-II recycling and prevention of lysosomal targeting, thereby stabilizing pMHC-II for antigen presentation. MHC-II ubiquitination mutant mice, biochemical recycling assays, lysosomal targeting assays, surface stability measurements in DCs and B cells Proceedings of the National Academy of Sciences of the United States of America High 26240324
2016 MARCH1 ubiquitinates the insulin receptor (INSR) to decrease cell surface INSR levels in the basal (non-stimulated) state, impairing insulin sensitivity. March1 loss-of-function enhances, and overexpression impairs, hepatic insulin sensitivity in mice. Unlike other INSR ubiquitin ligases, MARCH1 acts basally rather than after insulin stimulation. Large-scale RNAi screen, March1 KO mice, March1 overexpression mice, INSR ubiquitination assays, insulin clamp studies, flow cytometry for cell surface INSR Nature communications High 27577745
2018 MARCH1 indirectly regulates MHC I surface expression through its ubiquitination of MHC II. In MARCH1-deficient B cells and DCs, the altered MHC II trafficking (not direct MARCH1 ubiquitination of MHC I) causes reduced surface MHC I and impaired cross-presentation to CD8+ T cells. Deletion of MHC II in March1-/- cells restores normal MHC I surface expression. MARCH1 KO mice, MHC II KO in March1-/- background, flow cytometry, antigen cross-presentation assays to CD8+ T cells PloS one High 30001419
2018 MARCH1 promotes ubiquitin-dependent MHCII turnover that is required to maintain homeostasis of lipid rafts and the tetraspanin web in DC plasma membranes. Without MHCII ubiquitination, MHCII accumulates excessively in the plasma membrane, disrupting these membrane domains and impairing DC ability to engage thymocytes for Treg differentiation. MARCH1 KO and MHCII ubiquitination knockin mice, lipid raft fractionation, tetraspanin web analysis, Treg differentiation co-culture assays The Journal of cell biology High 29371232
2018 March-I is ubiquitinated on non-lysine residues (lysine-less March-I is ubiquitinated similarly to wild-type). March-I E3 ligase activity is not required for its own ubiquitination, indicating it does not autoubiquitinate itself. The E2 ubiquitin-conjugating enzyme Ube2D1 is required for March-I ubiquitination; Ube2D1 knockdown impairs March-I ubiquitination, increases March-I expression, and enhances March-I-dependent MHC-II downregulation. Lysine-less March-I mutant, catalytically inactive March-I mutant, Ube2D1 siRNA knockdown, ubiquitination assays, flow cytometry The Journal of biological chemistry High 29414787
2018 The March-I gene contains an APC-specific internal promoter driving expression of a distinct isoform in DCs and B cells. Downstream sequences in the first coding exon confer activation-induced down-regulation of March-I expression in DCs. These regulatory elements do not function in fibroblasts, kidney, or epithelial cells. March-I promoter-GFP reporter constructs, transfection in multiple cell types, LPS activation assays The Journal of biological chemistry Medium 29378848
2020 MARCH1 inhibits MAVS/STING/TRIF-induced type I IFN signaling in vitro and in vivo. In malaria-infected hosts, March1 deficiency paradoxically reduces IFN-I production by activating inhibitors (SOCS1, USP18, TRIM24) and altering immune cell populations, leading to increased IFN-γ and improved host survival that is reversed by T cell depletion or IFN-γ neutralization. March1 KO mice, Plasmodium yoelii infection model, transspecies eQTL genetic screen, MAVS/STING/TRIF reporter assays, cytokine measurements, T cell depletion, antibody neutralization Proceedings of the National Academy of Sciences of the United States of America Medium 32606244
2020 MARCH1 ubiquitination of MHC-II in DCs regulates DC gene expression and functional fitness. MHC-II ubiquitination-deficient DCs are poor stimulators of naive CD4 T cells and secrete IL-12 poorly in response to LPS despite high surface MHC-II. Single-cell RNA sequencing reveals these DCs have an altered gene expression signature that is reversed by LPS activation. MHC-II ubiquitination mutant mice, naive CD4 T cell stimulation assays, IL-12 ELISA, single-cell RNA sequencing Journal of immunology (Baltimore, Md. : 1950) High 33318291
2021 MARCH1 ubiquitin ligase regulates CD86 and MHC II in professional and atypical antigen presenting cells of hematopoietic origin (including neutrophils, eosinophils, and monocytes), whereas MARCH8 operates in non-hematopoietic cells. Unbiased plasma membrane proteomic profiling of primary cells from MARCH1-deficient mice identified CD86 and MHC II as the only substrates unequivocally regulated by MARCH1 in vivo. MARCH1 KO and MARCH8 KO mice, unbiased plasma membrane proteomics (mass spectrometry), flow cytometry across multiple cell types Current research in immunology High 35492398
2021 MARCH1-mediated ubiquitination of MHCII and CD86 on lymph node-resident DCs is required for TH2 cell development. Mice with mutations in the ubiquitin acceptor sites of both MHCII and CD86 fail to develop TH2 cells, demonstrating that clearance of antigen-presenting and costimulatory molecules by MARCH1 controls TCR signaling strength during TH2 polarization. MARCH1 KO mice, MHCII and CD86 ubiquitin-site knockin mice, in vivo TH2 differentiation assays, GATA-3 expression analysis Science immunology High 34652961
2021 MARCH1 promotes ubiquitination and degradation of HDAC11, which relieves HDAC11/KLF4-dependent repression of the OX40L gene promoter, thereby increasing OX40L expression in allergen-stimulated dendritic cells. Co-immunoprecipitation, immunofluorescence co-localization, luciferase OX40L promoter reporter assay, MARCH1 overexpression/knockdown, Western blot Journal of asthma and allergy Medium 34385821
2021 Human MARCH1 recognizes the CD86 transmembrane domain through a highly specific surface in the hydrophobic core featuring proline at position 254. This recognition mode is distinct from the viral MARCH homolog MIR2, which requires an aspartic acid in the CD86 extracellular juxtamembrane region and no specific TM sequences. Deep mutational scanning of CD86 TM domain, overexpression in cell lines, flow cytometry for surface CD86 The Journal of biological chemistry High 34157285
2022 MARCH1 ubiquitinates and promotes degradation of PHLPP2 in oral squamous cell carcinoma cells. Co-immunoprecipitation confirmed direct interaction between MARCH1 and PHLPP2. MARCH1 knockdown suppresses OSCC tumorigenicity in vivo and increases PHLPP2 protein levels. Co-immunoprecipitation, siRNA knockdown, overexpression, Western blot, in vivo xenograft model Clinical & translational oncology Medium 35122633
2022 MARCH1 isoform 1 (MARCH1.1) restricts influenza A virus (IAV) replication/infectivity, whereas isoform 2 (MARCH1.2) does not. Deletion of the entire N-terminal cytoplasmic domain of MARCH1.2, or specifically the 16 N-terminal residues, restores IAV restriction, mapping the difference in antiviral activity to the N-CT of MARCH1.2. Doxycycline-inducible overexpression system, viral titer assays, sequential N-CT deletion mutagenesis, qPCR for isoform expression Viruses Medium 36423158
2022 MARCH1 ubiquitinates and promotes degradation of the transferrin receptor (TfR), thereby regulating cellular iron levels during human cytomegalovirus (HCMV) infection. MARCH1 knockdown decreases infectious HCMV titers, increases ROS, lipid peroxidation, and mitochondrial dysfunction, establishing a proviral role for MARCH1 in regulating iron metabolism. MARCH1 knockdown (siRNA), TfR expression analysis, labile iron pool measurement, ROS and lipid peroxidation assays, viral titer assays Journal of virology Medium 35045264
2023 MARCHF1 acts as an E3 ubiquitin ligase for GPX4, promoting its ubiquitination and degradation, thereby increasing susceptibility to ferroptosis. BaP/BPDE exposure up-regulates MARCHF1 expression, leading to GPX4 protein degradation and consequent suppression of HUVEC angiogenesis and induction of miscarriage. Ubiquitination assays, MARCHF1 overexpression/knockdown in HUVECs, GPX4 protein level measurement, angiogenesis assays, mouse BaP exposure miscarriage model Environment international Medium 37802009
2024 Human MARCH1 and MARCH2 retain Ebola virus (EBOV) glycoprotein (GP) at the trans-Golgi network, reduce its cell surface display, and impair EBOV GP-pseudotyped virion infectivity by blocking furin-mediated cleavage. The furin P domain is recognized by MARCH1/2/8 and is critical for their blocking activities. Host furin interacts with MARCH1/2 and EBOV GP intracellularly. Co-immunoprecipitation of furin with MARCH1/2 and EBOV GP, EBOV GP-pseudotyped viral infection assays, furin P domain mutagenesis, subcellular localization analysis Journal of medical virology Medium 38299743
2024 MARCH1 interacts with TBK1 and promotes K63-linked ubiquitination of TBK1, attenuating TBK1 interaction with mTOR and thereby inhibiting growth factor-induced mTOR signaling. MARCH1 deficiency accelerates breast cancer cell proliferation, which is reversed by inhibition of mTOR, STING, or TBK1. Co-immunoprecipitation, denatured Co-IP ubiquitination assays, Western blot, shRNA knockdown, lentiviral overexpression, scratch wound and colony assays BMC cancer Medium 39061024
2024 MARCH1 mediates ubiquitination and degradation of PCSK9, lowering PCSK9 protein expression, and thereby suppresses inflammation and pyroptosis in cerebral ischemia-reperfusion injury. Mechanistically, PCSK9 knockdown reduces brain damage, upregulates LDLR, and inactivates the NLRP3 inflammasome. Co-immunoprecipitation, cycloheximide degradation assay, MARCH1/PCSK9 overexpression/knockdown, MCAO/R mouse model, OGD/R neuron model Mammalian genome Medium 39115562
2025 CD83 suppresses endogenous March-I-dependent MHC-II ubiquitination, endocytosis, and degradation in mouse spleen DCs. Endogenous March-I protein is present at extremely low copy numbers (~500 molecules/cell in DCs, ~125 in B cells), has a very short half-life, and March-I mRNA, protein, and MHC-II ubiquitination are all rapidly terminated upon DC or B cell activation. V5-epitope knock-in into endogenous March-I locus, quantitative flow cytometry, MHC-II ubiquitination assays, pulse-chase half-life, LPS activation of primary spleen DCs and B cells Proceedings of the National Academy of Sciences of the United States of America High 40397676
2025 MARCHF1 promotes GABAB receptor downregulation under ischemic/excitotoxic conditions by interacting with GABAB receptors and inhibiting fast receptor recycling at the plasma membrane, leading to progressive neuronal death. An interfering peptide blocking the MARCH1/GABAB receptor interaction restores receptor surface expression and prevents neuronal death. Co-immunoprecipitation, interfering peptide competition, surface GABAB receptor quantification in ischemic neurons, neuronal death assays Scientific reports Medium 39779794
2025 MARCHF1 interacts with SARS-CoV-2 M protein and mediates ubiquitination and degradation of GPX4, contributing to ferroptosis during SARS-CoV-2 infection. The M-GPX4 interaction occurs at the R72 residue of GPX4. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis of GPX4 R72, ferroptosis assays in infected cells Journal of medical virology Medium 40186530
2025 MARCH1 interacts with MYCT1 (a candidate tumor suppressor) and promotes its K48-linked ubiquitination and degradation, facilitating AML cell proliferation and survival. POU2F2 transcription factor positively regulates MARCH1 transcription in AML. MYCT1 knockdown abolishes the inhibitory effects of MARCH1 knockdown on AML cell growth. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, gain- and loss-of-function experiments, in vivo AML mouse model Oncogene Medium 40533483
2025 MARCHF1 ubiquitinates and promotes degradation of SULF1 in colon cancer cells, thereby blocking SULF1-THBS2 interaction and suppressing TGF-β1/SMAD2/3 pathway activation, which leads to reduced tumor metastasis and enhanced sensitivity to 5-FU. Co-immunoprecipitation, ubiquitination assays, MARCHF1 and SULF1 knockdown/overexpression, TGF-β pathway analysis, drug sensitivity assays iScience Medium 41550717
2025 MARCHF1 interacts with and promotes ubiquitination and degradation of REST (repressor element-1 silencing transcription factor), reducing REST protein levels and consequently de-repressing TFAM transcription, promoting mitochondrial function and breast cancer cell proliferation. Co-immunoprecipitation, ubiquitination assays, MARCHF1 knockdown/overexpression, Western blot for REST and TFAM, in vivo xenograft model Cell biology international Medium 39428668
2026 MARCH1 directly binds to KLF15 (Krüppel-like factor 15) in white adipose tissue, contributing to HFpEF pathogenesis. MARCH1 deficiency induces WAT beiging and alleviates cardiac dysfunction in a HFpEF mouse model; overexpressing KLF15 blocks the beiging effects of MARCH1 KO. Co-immunoprecipitation, MARCH1 KO HFpEF mouse model, RNA sequencing, echocardiography, histology, KLF15 overexpression rescue Comprehensive Physiology Medium 41986908
2026 MARCH1 promotes ubiquitination and degradation of SLC25A17, a mitochondrial transporter. MARCH1 overexpression suppresses macrophage M2 polarization and DDP resistance in lung adenocarcinoma; SLC25A17 overexpression reverses the DDP sensitivity enhancement caused by MARCH1 reintroduction. Co-immunoprecipitation, ubiquitination assays, MARCH1 overexpression/knockdown, SLC25A17 rescue overexpression, flow cytometry, ELISA, in vivo tumor model Integrative biology Medium 41758657

Source papers

Stage 0 corpus · 72 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. Proceedings of the National Academy of Sciences of the United States of America 205 18305173
2011 CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation. The Journal of experimental medicine 188 21220452
2015 Interleukin 10 (IL-10)-mediated Immunosuppression: MARCH-I INDUCTION REGULATES ANTIGEN PRESENTATION BY MACROPHAGES BUT NOT DENDRITIC CELLS. The Journal of biological chemistry 140 26408197
2008 Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes. European journal of immunology 138 18389477
2016 MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels. Nature communications 75 27577745
2013 Antigen-specific induced T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism. Journal of immunology (Baltimore, Md. : 1950) 71 24218453
2013 MARCH1-mediated MHCII ubiquitination promotes dendritic cell selection of natural regulatory T cells. The Journal of experimental medicine 69 23712430
2023 BaP/BPDE suppressed endothelial cell angiogenesis to induce miscarriage by promoting MARCHF1/GPX4-mediated ferroptosis. Environment international 63 37802009
2015 Ubiquitination by March-I prevents MHC class II recycling and promotes MHC class II turnover in antigen-presenting cells. Proceedings of the National Academy of Sciences of the United States of America 58 26240324
2009 Discrete domains of MARCH1 mediate its localization, functional interactions, and posttranscriptional control of expression. Journal of immunology (Baltimore, Md. : 1950) 56 19880452
2009 Cutting edge: requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance of conventional dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 55 19917682
2019 Goat membrane associated ring-CH-type finger 1 (MARCH1) mRNA expression and association with litter size. Theriogenology 47 30711644
2016 Silencing MARCH1 suppresses proliferation, migration and invasion of ovarian cancer SKOV3 cells via downregulation of NF-κB and Wnt/β-catenin pathways. Oncology reports 41 27633480
2012 Autoregulation of MARCH1 expression by dimerization and autoubiquitination. Journal of immunology (Baltimore, Md. : 1950) 39 22508929
2020 The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation. Proceedings of the National Academy of Sciences of the United States of America 38 32606244
2018 MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway. PloS one 36 30001419
2020 Resveratrol inhibits the malignant progression of hepatocellular carcinoma via MARCH1-induced regulation of PTEN/AKT signaling. Aging 35 32530437
2012 Francisella tularensis elicits IL-10 via a PGE₂-inducible factor, to drive macrophage MARCH1 expression and class II down-regulation. PloS one 34 22615981
2019 Secalonic Acid-F, a Novel Mycotoxin, Represses the Progression of Hepatocellular Carcinoma via MARCH1 Regulation of the PI3K/AKT/β-catenin Signaling Pathway. Molecules (Basel, Switzerland) 33 30678274
2016 MARCH1 E3 Ubiquitin Ligase Dampens the Innate Inflammatory Response by Modulating Monocyte Functions in Mice. Journal of immunology (Baltimore, Md. : 1950) 33 27940660
2018 March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity. Nature communications 32 30154416
2018 Ubiquitin-conjugating enzyme E2 D1 (Ube2D1) mediates lysine-independent ubiquitination of the E3 ubiquitin ligase March-I. The Journal of biological chemistry 29 29414787
2020 5-FU inhibits migration and invasion of CRC cells through PI3K/AKT pathway regulated by MARCH1. Cell biology international 28 33085122
2012 MARCH1 down-regulation in IL-10-activated B cells increases MHC class II expression. Cytokine 27 22503116
2021 Myricetin Induces Autophagy and Cell Cycle Arrest of HCC by Inhibiting MARCH1-Regulated Stat3 and p38 MAPK Signaling Pathways. Frontiers in pharmacology 25 34733155
2017 Genetic effects of PDGFRB and MARCH1 identified in GWAS revealing strong associations with semen production traits in Chinese Holstein bulls. BMC genetics 25 28673243
2021 Lymph node-resident dendritic cells drive TH2 cell development involving MARCH1. Science immunology 21 34652961
2019 ciRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653. Aging 21 31819015
2021 Sinomenine Suppresses Development of Hepatocellular Carcinoma Cells via Inhibiting MARCH1 and AMPK/STAT3 Signaling Pathway. Frontiers in molecular biosciences 19 34179090
2018 March1 E3 Ubiquitin Ligase Modulates Features of Allergic Asthma in an Ovalbumin-Induced Mouse Model of Lung Inflammation. Journal of immunology research 19 29854835
2024 Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain. Journal of medical virology 18 38299743
2010 MARCH-I: a new regulator of dendritic cell function. Molecules and cells 18 20213309
2018 The E3 ubiquitin ligase MARCH1 regulates glucose-tolerance and lipid storage in a sex-specific manner. PloS one 17 30356278
2018 MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells. The Journal of cell biology 16 29371232
2022 MARCH1 silencing suppresses growth of oral squamous cell carcinoma through regulation of PHLPP2. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 13 35122633
2020 Ubiquitination of MHC Class II by March-I Regulates Dendritic Cell Fitness. Journal of immunology (Baltimore, Md. : 1950) 13 33318291
2013 Tollip-induced down-regulation of MARCH1. Results in immunology 13 24600555
2025 Curcumin Inhibits the Growth of Hepatocellular Carcinoma via the MARCH1-mediated Modulation of JAK2/STAT3 Signaling. Recent patents on anti-cancer drug discovery 12 38243928
2012 Identification of a novel motif that affects the conformation and activity of the MARCH1 E3 ubiquitin ligase. Journal of cell science 11 23264739
2023 Regulation of MHC class II and CD86 expression by March-I in immunity and disease. Current opinion in immunology 10 37075597
2022 The Immune-Specific E3 Ubiquitin Ligase MARCH1 Is Upregulated during Human Cytomegalovirus Infection to Regulate Iron Levels. Journal of virology 10 35045264
2021 Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8. Current research in immunology 10 35492398
2018 A major isoform of the E3 ubiquitin ligase March-I in antigen-presenting cells has regulatory sequences within its gene. The Journal of biological chemistry 10 29378848
2011 Environmental epigenomics and disease susceptibility. Keystone symposia on molecular and cellular biology. The Grove Park Hotel & Spa, Ashville, NC, USA, 27 March–1 April 2011. Epigenomics 10 22122336
2021 Human and viral membrane-associated E3 ubiquitin ligases MARCH1 and MIR2 recognize different features of CD86 to downregulate surface expression. The Journal of biological chemistry 9 34157285
2021 E3 Ubiquitin Ligase March1 Facilitates OX40L Expression in Allergen-Stimulated Dendritic Cells Through Mediating the Ubiquitination of HDAC11. Journal of asthma and allergy 9 34385821
2024 E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation. Mammalian genome : official journal of the International Mammalian Genome Society 8 39115562
2013 Altered MARCH1 ubiquination-regulated dendritic cell immune functions during the early stage of zymosan-induced multiple organ dysfunction syndrome (MODS) in mice. Immunology letters 8 23305794
2024 MARCH1 and MARCH2 inhibit pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in trans-Golgi network. Veterinary microbiology 7 38936155
2023 MicroRNA-25/93 induction by Vpu as a mechanism for counteracting MARCH1-restriction on HIV-1 infectivity in macrophages. mBio 7 37773002
2023 Exosome‑delivered miR‑486‑3p inhibits the progression of osteosarcoma via sponging CircKEAP1/MARCH1 axis components. Oncology letters 7 38058466
2022 Isoforms of Human MARCH1 Differ in Ability to Restrict Influenza A Viruses Due to Differences in Their N Terminal Cytoplasmic Domain. Viruses 7 36423158
2022 MARCH1 promotes the growth and maintaining of stem cell-like characteristics of gastric cancer cells by activating the Wnt/β-catenin signaling pathway. Tissue & cell 6 35985246
2021 March1-overexpressed dendritic cells downregulate Th1/Th2 ratio in asthma through promoting OX40L. International immunopharmacology 6 34923421
2024 MARCH1 negatively regulates TBK1-mTOR signaling pathway by ubiquitinating TBK1. BMC cancer 5 39061024
2025 SARS-CoV-2 Membrane Protein Induces MARCHF1/GPX4-Mediated Ferroptosis by Promoting Lipid Accumulation. Journal of medical virology 4 40186530
2022 MARCH1 Controls an Exhaustion-like Program of Effector CD4+ T Cells Promoting Allergic Airway Inflammation. ImmunoHorizons 4 36100368
2020 Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice. Frontiers in immunology 4 32973799
2025 The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABAB receptors under ischemic conditions by inhibiting fast receptor recycling. Scientific reports 3 39779794
2022 Targeting psychological stress-steroid-MARCH1 signaling pathway promotes the efficacy of specific allergen immunotherapy. Theranostics 3 36451862
2025 MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation. Oncogene 2 40533483
2024 MARCH-I: A negative regulator of dendritic cell maturation. Experimental cell research 2 38331309
2022 Induced overexpression of MARCH-1 in human macrophages altered to M2 phenotype for suppressing inflammation process. Iranian journal of basic medical sciences 2 35656075
2021 A Novel 4q32.3 Deletion in a Child: Additional Signs and the Role of MARCH1. Journal of pediatric genetics 2 34853711
2025 CD83 suppresses endogenous March-I-dependent MHC class II ubiquitination, endocytosis, and degradation. Proceedings of the National Academy of Sciences of the United States of America 1 40397676
2024 MARCHF1 promotes breast cancer through accelerating REST ubiquitylation and following TFAM transcription. Cell biology international 1 39428668
2021 RON Expression Mediates Lipopolysaccharide-Mediated Dendritic Cell Maturation via March-I. Frontiers in cellular and infection microbiology 1 33537243
2011 MARCH-I expression in cord blood CD34+KDR+ cells. Clinical biochemistry 1 21385572
2026 MARCH1 attenuates lung adenocarcinoma by blocking macrophage M2 polarization and cisplatin resistance through reducing SLC25A17 stability. Integrative biology : quantitative biosciences from nano to macro 0 41758657
2026 MARCH1 Deletion Attenuates HFpEF by Promoting Adipose Beiging. Comprehensive Physiology 0 41986908
2025 HIV-2 glycoproteins upregulate microRNAs 25 and 93 to counter the MARCH1 antiviral effect in macrophages. Journal of virology 0 41283654
2025 MARCHF1-mediated SULF1 degradation blocks THBS2/TGF-β/SMAD2/3 signaling to reverse colon cancer metastasis and 5-FU resistance. iScience 0 41550717

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