| 2009 |
MARCH9 is a RING-CH transmembrane E3 ubiquitin ligase that down-regulates multiple plasma membrane proteins in lymphoid cells, including CD4, MHC-I, ICAM-1, PTPRJ/CD148, CD32B, HLA-DQ, CD150, and CD155, as identified by SILAC-based quantitative plasma membrane proteomics combined with flow cytometry confirmation. |
SILAC quantitative mass spectrometry of plasma membrane proteome in MARCH9-expressing B cell line, confirmed by flow cytometry |
Molecular & cellular proteomics : MCP |
High |
19457934
|
| 2010 |
MARCH9 (and MARCH4) ubiquitinates the NKG2D ligand Mult1, suppressing its cell-surface expression; lysines in the cytoplasmic tail of Mult1 are essential for this repression. Heat-shock treatment dissociates Mult1 from MARCH9, reversing down-regulation and increasing Mult1 at the cell surface. |
Co-immunoprecipitation, flow cytometry, lysine mutant analysis, heat-shock functional assay |
Journal of immunology |
High |
20870941
|
| 2012 |
MARCH9 ubiquitinates HLA-DM via a single lysine in the cytoplasmic tail of the DMα chain, inducing loss of DM from the cell surface by a mechanism involving both direct ubiquitin-chain attachment to DMα and a functional tyrosine-based signal on DMβ. |
Transfection/overexpression, flow cytometry, mutational analysis of acceptor lysine and tyrosine-based signal |
The Journal of biological chemistry |
Medium |
22247549
|
| 2012 |
MARCH9 substrate specificity for HLA-DQ (versus MARCH8 preference for HLA-DR) is determined by residues at the interface of the transmembrane domain and cytosol of the HLA β-chain; the acceptor lysine functions optimally at its natural position relative to the bilayer. |
Mutagenesis and chimeric construct analysis of HLA-DR/DQ transmembrane and cytoplasmic tail residues, flow cytometry readout |
The Journal of biological chemistry |
Medium |
22761441
|
| 2017 |
MARCH9 ubiquitinates the cytoplasmic tail lysine residues of MHC-I, redirecting MHC-I from the default secretory pathway to Syntaxin 6-positive endosomal compartments at the trans-Golgi network, thereby regulating MHC-I export from the TGN. MARCH9 also targets CD1a. MARCH9 expression is modulated by microbial pattern exposure in dendritic cells. |
Overexpression/knockdown of MARCH9, co-localization with Syntaxin 6 by microscopy, MHC-I ubiquitination assay, flow cytometry, stimulation of dendritic cells with microbial patterns |
Immunology and cell biology |
High |
28559542
|
| 2018 |
A single serine-to-alanine substitution in the first transmembrane domain (TM1) of human MARCH9 completely abolishes its ability to down-regulate HLA-A2 and CD4, identifying this serine as critical for substrate regulation. Solution NMR of the MARCH9 two-TM fragment shows that residues closest to the extracellular face of TM1 and TM2 define the key functional region. |
Site-directed mutagenesis of MARCH9 TM domains, flow cytometry functional assay, solution NMR of TM domain fragment |
The Journal of biological chemistry |
High |
30554144
|
| 2018 |
MARCH9 interacts with ICAM-1 and overexpression of MARCH9 down-regulates ICAM-1 protein, attenuating migration and invasion of lung adenocarcinoma cells. |
Co-immunoprecipitation, overexpression in A549 and H1299 cells, flow cytometry/western blot, migration/invasion assays |
Cellular physiology and biochemistry |
Medium |
30278450
|
| 2019 |
MARCH9 (along with MARCH2, MARCH4, and an isoform of MARCH3) down-regulates the IL-6 receptor alpha chain (IL6Rα) at the cell surface; functional RING domain, transmembrane domains, and C-terminal domains are all required for substrate recognition and down-regulation. |
cDNA expression library screen, overexpression in M1 cells, domain deletion/mutagenesis constructs, flow cytometry |
The Biochemical journal |
Medium |
31488575
|
| 2021 |
Tim-3 signaling in macrophages promotes MARCH9 expression, which in turn mediates K48-linked ubiquitination of MHC-I (HLA class I), leading to its proteasome-dependent degradation and reduced surface MHC-I presentation. |
Western blot, co-immunoprecipitation, ubiquitination assay (K48-linkage specific), Tim-3 antibody treatment and macrophage depletion in vivo |
Frontiers in immunology |
Medium |
34025669
|
| 2022 |
Under heat stress, MARCH9 promotes K63-linked ubiquitination of ATG9A at the TGN, causing ubiquitinated ATG9A to disperse from the Golgi to the cytoplasm, inhibiting GRASP55 oligomerization and resulting in Golgi fragmentation. Knockout of MARCH9 prevents heat-stress-induced Golgi fragmentation. |
Co-immunoprecipitation, K63-specific ubiquitination assay, MARCH9 knockout cells, Golgi morphology imaging under heat stress |
Cell reports |
High |
35977480 36198086
|
| 2022 |
MARCH9 (MARCHF9) promotes colorectal cancer cell proliferation and migration by downregulating the deubiquitinase CYLD and activating NF-κB (p65); knockdown of MARCH9 induces apoptosis and cell-cycle arrest, and suppresses xenograft tumor growth. |
MARCH9 knockdown/overexpression, western blot for CYLD and p65, apoptosis/cell cycle flow cytometry, xenograft in vivo model |
Frontiers in oncology |
Low |
36185211
|
| 2023 |
MARCH9 mediates ubiquitination and degradation of NADPH oxidase-2 (NOX2), reducing ROS accumulation and NLRP3 inflammasome activation, thereby suppressing pancreatic cell pyroptosis in acute pancreatitis. |
MARCH9 overexpression in AR42J cells and cerulein-induced rat model, flow cytometry for ROS, western blot for NLRP3/caspase-1/GSDMD, ubiquitination assay for NOX2 |
Pancreas |
Medium |
37378901
|
| 2024 |
LILRB2 promotes MARCH9–HLA-A (HLA-A ubiquitin ligase) interaction, facilitating ubiquitination and proteasomal degradation of HLA-A, thereby enabling breast cancer immune evasion by reducing surface MHC-I presentation to CD8+ T cells. |
Co-immunoprecipitation, histidine pulldown ubiquitination assay, western blot, syngeneic mouse tumor model |
Cellular oncology |
Medium |
38656573
|
| 2025 |
MARCH9 interacts with NLRP3 and promotes its K48-linked polyubiquitination, leading to proteasomal degradation of NLRP3, thereby inhibiting inflammasome activation and pyroptosis during myocardial ischemia-reperfusion injury. |
Co-immunoprecipitation, K48-linkage-specific ubiquitination assay, western blot, mouse MI/R in vivo model, H9C2 and HEK293 cell in vitro studies |
Cellular and molecular life sciences : CMLS |
Medium |
41055760
|
| 2025 |
ETV4 transcriptionally upregulates MARCH9, which then mediates K63-linked ubiquitination of the mitochondrial fusion protein Mfn2, targeting it for lysosomal degradation and impairing mitochondrial fusion in ovarian cancer cells. |
ETV4 silencing, MARCH9 overexpression rescue, western blot for Mfn2, lysosomal inhibitor (chloroquine) block, K63-ubiquitination assay |
Cell biology and toxicology |
Medium |
41114773
|
| 2026 |
RBM10 recruits MARCHF9 to catalyze K33-linked ubiquitination of PEDV nonstructural protein 3 (Nsp3); the ubiquitinated Nsp3 is then recognized by the selective autophagy receptor p62 and delivered to autophagosomes for degradation, restricting viral replication. |
LC-MS/MS interaction screen, functional knockdown/overexpression assays, autophagic flux blockade, p62 knockdown, K33-linkage ubiquitination assay |
Veterinary microbiology |
Medium |
42229174
|