| 1997 |
ARPC4 (p20-Arc) was identified as one of seven subunits of the human Arp2/3 complex; the complex localizes to lamellipodia of fibroblasts and Listeria actin tails (but not actin bundles), consistent with a role in promoting actin assembly at sites of dynamic polymerization. |
Protein purification, sequencing, immunofluorescence localization in cells |
The Journal of cell biology |
High |
9230079
|
| 2001 |
Crystal structure of bovine Arp2/3 complex at 2.0 Å resolution revealed that ARPC4 (p20) and ARPC2 (p34) form the core of the complex through long C-terminal alpha helices and similarly folded N-terminal alpha/beta domains. |
X-ray crystallography at 2.0 Å resolution |
Science (New York, N.Y.) |
High |
11721045
|
| 2001 |
Yeast two-hybrid analysis showed that p20-Arc (ARPC4) acts as a hub for subunit interactions within the human Arp2/3 complex, interacting with p21-Arc (ARPC3), p34-Arc (ARPC2), and p16-Arc (ARPC5); p41-Arc only interacted with the p20-Arc/p16-Arc heterodimer. Structural integrity was important for p20-Arc/p21-Arc association, while the N-terminal half of p34-Arc was dispensable for its binding to p20-Arc. |
Yeast two-hybrid assay |
Biochemical and biophysical research communications |
Medium |
11162547
|
| 2010 |
Molecular dynamics and protein-protein docking simulations, validated by mutagenesis, defined an actin-filament-binding interface on ARPC2 and ARPC4. Residues at this interface are required for actin nucleation, Y-branching, high-affinity F-actin binding, and Y-branch stability, demonstrating that Arp2/3 complex affinity for F-actin independently modulates branch formation and stability. |
Molecular dynamics/docking simulations + mutagenesis + in vitro actin assembly assays + F-actin binding assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
20404198
|
| 2010 |
Molecular dynamics simulations of Arp2/3 activation showed that one structural block (comprising Arp2, ARPC1, the globular domain of ARPC4, and ARPC5) rotates ~30° around a pivot point in an alpha-helix of ARPC4 (Glu81–Asn100) to bring Arp2 into proximity with Arp3 during activation. |
Atomistic molecular dynamics simulations |
Biophysical journal |
Low |
20959098
|
| 2011 |
Phosphorylation of Arp2 destabilizes a network of auto-inhibitory salt-bridge interactions at the interface of Arp2, Arp3, and ARPC4, permitting Arp2 reorientation to an activation-competent state. A gain-of-function ARPC4 mutant predicted to disrupt these interactions showed substantial actin nucleation activity in the absence of NPFs. |
Molecular dynamics simulations + biochemical assays with recombinant Arp2/3 complex carrying ARPC4 mutations |
PLoS computational biology |
Medium |
22125478
|
| 2009 |
Hydrogen/deuterium exchange mass spectrometry showed that ATP binding to Arp2/3 complex causes conformational rearrangements in Arp2 and Arp3 that are allosterically transmitted to ARPC4 (and ARPC1, ARPC2, ARPC5); WASp VCA binding further modulates exchange rates in ARPC4, indicating global conformational reorganization involving this subunit upon activation. |
Hydrogen/deuterium exchange coupled with mass spectrometry |
Journal of molecular biology |
Medium |
19298826
|
| 2008 |
In S. cerevisiae, a contact surface between p35/ARPC2 and p19/ARPC4 was identified as required for actin nucleation and endocytosis; mutations near this interface abolished nucleation without disrupting complex integrity. |
Systematic mutagenesis in S. cerevisiae + purification of mutant complexes + in vitro actin assembly assays + endocytosis assays |
The Journal of biological chemistry |
High |
18381280
|
| 2010 |
In S. cerevisiae, lethal mutations at the p40/ARPC1 contact with p19/ARPC4 specifically impaired WASp-induced nucleation of purified Arp2/3 complex, placing ARPC4 at the interface required for WASp activation signal propagation. |
Mutagenesis of ARPC1 + purification of mutant complexes + in vitro actin nucleation assays |
The Journal of biological chemistry |
High |
20071330
|
| 2017 |
Conditional knockout of Arpc4 in mouse epidermis depleted the Arp2/3 complex and caused a psoriasis-like disease; Arpc4 knockout in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2 target genes, and decreased F-actin levels. In vitro, Nrf2 was shown to bind to filamentous actin. |
Conditional Arpc4 knockout mouse model + keratinocyte culture KO + pharmacological Arp2/3 inhibition + in vitro F-actin binding assay |
Development (Cambridge, England) |
High |
29113991
|
| 2021 |
Conditional ablation of Arpc4 in mouse pancreatic acinar cells demonstrated that the Arp2/3 complex is required for KrasG12D-driven acinar-to-ductal metaplasia (ADM) in vivo; mTORC1 regulates Arp2/3 complex activity via Rac1/Arp3 translation while mTORC2 promotes Arp2/3 via Akt/Rac1, converging on ARPC4-containing Arp2/3 as a common downstream effector for actin cortex remodeling and ADM. |
Conditional Arpc4 knockout mouse + in vitro ADM assays + epistasis with Rptor/Rictor conditional knockouts |
Gastroenterology |
High |
33388318
|
| 2021 |
A recurrent de novo missense variant in ARPC4 (p.Arg158Cys) found in patients with microcephaly and speech delay was associated with decreased F-actin levels in cells from affected individuals, implicating ARPC4 in actin filament network formation required for neurodevelopment. |
Patient cell-based F-actin quantification (immunofluorescence/imaging) in cells from affected individuals carrying the variant |
HGG advances |
Medium |
35047857
|
| 2025 |
UFL1 (UFM1-specific E3 ligase 1) interacts with ArpC4 and catalyzes its UFMylation. Akt phosphorylates UFL1 at T426, which enhances UFL1's interaction with ArpC4 and promotes ArpC4 UFMylation, thereby facilitating lamellipodia formation, cell migration, invasion, and metastasis. |
Co-immunoprecipitation, in vitro UFMylation assay, phosphorylation mapping, loss-of-function cell migration/invasion assays, lamellipodia imaging |
Nature structural & molecular biology |
High |
40419786
|
| 2022 |
Binary clostridial toxins (CDT, C2I, Iota) ADP-ribosylate ARPC4/5 (among other Arp2/3 subunits) in addition to actin and Arp2, and this modification inhibits Arp2/3 complex actin-nucleating activity, causing collapse of lamellipodia and F-actin networks in cells. |
Mass spectrometry identification of ADP-ribosylation sites + in vitro Arp2/3 activity assays + cell imaging (Caco2 cells + mouse colon explants) |
Cells |
Medium |
36429089
|
| 2013 |
siRNA-mediated silencing of ARPC4 significantly reduced cell migration (50–68% decrease) in pancreatic cancer cell lines without affecting other processes, indicating ARPC4 is a key functional subunit for Arp2/3-dependent migration in these cells. |
siRNA knockdown + transwell migration assay in multiple pancreatic cancer cell lines |
Anticancer research |
Medium |
23267127
|
| 2019 |
ARPC4 knockdown in T24 bladder cancer cells attenuated migration, invasion, and pseudopodia formation and disrupted actin cytoskeleton structure, demonstrating a direct role of ARPC4 in actin-dependent invasive behavior. |
siRNA knockdown + transwell invasion/migration assay + wound-healing assay + immunofluorescence of actin cytoskeleton |
Journal of cellular biochemistry |
Medium |
31190401
|
| 2016 |
Chemical cross-linking/mass spectrometry identified the entire seven-subunit Arp2/3 complex (including ARPC4) as an interaction partner of human PKD2 in both cytosolic and Golgi-enriched fractions, with evidence of a direct protein-protein interaction between PKD2 and Arp2/3. |
Affinity enrichment + chemical cross-linking + mass spectrometry |
Journal of proteome research |
Low |
27559607
|
| 2013 |
Expression of ARPC4 in Mycobacterium tuberculosis severely impaired bacterial growth (evidenced by TEM showing outer-coat shedding), enhanced bacterial clearance in infected macrophages, impaired phagosome-to-lysosome translocation, and suppressed pro-inflammatory cytokine responses. ARPC4 was shown to interact with the essential mycobacterial secretory protein Rv1626, downregulating its expression ~6-fold; Rv1626 also interacted with mammalian Arp2/3 and enhanced actin polymerization. |
Bacterial expression of ARPC4 + TEM + macrophage infection assays + co-immunoprecipitation (ARPC4–Rv1626 interaction) + real-time PCR |
PloS one |
Medium |
23894563
|
| 2016 |
Viral protein Ac34 (baculovirus) co-immunoprecipitated with ARPC4 (P20) of Sf9 (insect) cells and induced its nuclear relocation; however, mammalian ARPC4 did not interact with Ac34 and was not relocated, indicating species-specific binding specificity. |
Immunofluorescence + co-immunoprecipitation |
Virologica Sinica |
Low |
27900558
|
| 2025 |
In cervical cancer cells, Aurora-A overexpression upregulated ARPC4 expression via activation of the NF-κBp65 signaling pathway (increased NF-κBp65 phosphorylation led to elevated ARPC4 levels), and ARPC4 knockdown antagonized Aurora-A-promoted migration, invasion, and EMT. |
Plasmid overexpression + shRNA knockdown + NF-κBp65 inhibitor treatment + Western blot + migration/invasion assays |
Nan fang yi ke da xue xue bao |
Medium |
40294934
|
| 2019 |
A genome-wide CRISPR knockout screen in THP-1 macrophages identified ARPC4 loss-of-function as conferring resistance to Salmonella uptake, placing ARPC4-containing Arp2/3 complex in the actin dynamics pathway required for macrophage phagocytic internalization of bacteria. |
Genome-wide CRISPR KO screen + validation assays |
mBio |
Medium |
31594818
|
| 2025 |
In a gut epithelium-specific inducible Arpc4 knockout mouse, loss of Arp2/3 function led to increased intestinal permeability, disrupted tight junction protein localization, epithelial fracturing, and lethality under mechanical challenge; ex vivo organoid experiments showed defects required mechanical stress and elevated actomyosin contractility to manifest. |
Inducible conditional Arpc4 KO mouse + ex vivo intestinal slice culture + organoid culture + tight junction imaging |
Current biology : CB |
High |
40930096
|
| 2026 |
Conditional Arpc4 knockout in myeloid cells showed that Arp2/3 complex loss in Langerhans cells leads to cell decline through DNA damage accumulation associated with aberrant nuclear shapes, lamina reduction, and nuclear envelope rupture, revealing a role for Arp2/3/ARPC4 in nuclear envelope integrity and genome maintenance in tissue-resident immune cells. |
Conditional Arpc4 KO mouse + in vivo LC analysis + in vitro BMDC experiments + cell cycle analysis + nuclear morphology/DNA damage assays |
bioRxivpreprint |
Medium |
|
| 2026 |
Conditional Arpc4 knockout in microglia showed that Arp2/3 depletion prevents the developmental transition of microglia into ramified cells with homeostatic gene profiles and surveillance function, linking ARPC4-dependent actin branching to microglial maturation in the CNS. |
Conditional Arpc4 KO mouse + morphological analysis + transcriptomic profiling of microglia + CNS surveillance assays |
EMBO reports |
High |
41760937
|
| 2026 |
CRISPR/Cas9 knockout of Arpc4 in murine PDAC cell lines downregulated all Arp2/3 complex members and significantly impaired PDAC cell migration, disrupted branched tubular structure formation in collagen I, and inhibited invasive front formation in organoid culture; β1 integrin signaling was identified as a key upstream regulator of Arp2/3-dependent migration through collagen-rich matrices. |
CRISPR/Cas9 KO + 2D and 3D migration/invasion assays + organoid co-culture + β1 integrin signaling analysis |
International journal of cancer |
Medium |
41793310
|
| 2026 |
ArpC4 knockdown by siRNA in U2OS cells reduced HDR efficiency, but this effect corresponded with decreased transfection efficiency and reduction in S/G2M cell cycle phases rather than a direct role in DNA repair; WASP/N-WASP were found dispensable for HDR. |
siRNA knockdown + CRISPR-based HDR reporter assay + cell cycle analysis |
EMBO reports |
Medium |
41963733
|