| 2013 |
MISP (C19orf21) is a substrate of Plk1; Plk1 phosphorylates MISP, and this phosphorylation is required for the metaphase-to-anaphase transition and proper mitotic spindle positioning. MISP is an actin-associated protein that forms a complex with p150(glued) (a dynein-dynactin subunit) and regulates its cortical distribution, thereby stabilizing cortical and astral microtubule attachments. |
Loss-of-function (siRNA depletion), phosphorylation assays identifying Plk1 as the kinase, co-immunoprecipitation of MISP with p150(glued), live-cell imaging of spindle orientation and astral microtubule length |
The Journal of cell biology |
High |
23509069
|
| 2013 |
MISP associates with the actin cytoskeleton and focal adhesions and is expressed only in adherent cell types. During mitosis, MISP is phosphorylated by Cdk1 and localizes to retraction fibers. MISP interacts with the +TIP protein EB1 and with p150(glued) (dynein/dynactin). Depletion of MISP causes mitotic arrest with reduced tension across sister kinetochores, chromosome misalignment, spindle multipolarity (in cells with supernumerary centrosomes), and randomized spindle orientation. |
Co-immunoprecipitation (MISP with EB1 and p150glued), Cdk1 phosphorylation assay, siRNA depletion with live-cell imaging, immunofluorescence of focal adhesions and retraction fibers, kinetochore tension measurements |
Cell cycle (Georgetown, Tex.) |
High |
23574715
|
| 2014 |
MISP/Caprice is a direct actin-binding protein with multiple actin-binding sites that forms mesh-like F-actin bundles in vitro. Overexpression induces stress fiber-like thick filaments and knockdown causes filopodial formation, demonstrating a direct role in actin cytoskeletal organization. It is expressed in cells/tissues with specialized actin structures such as growth cones and inner ear hair cell stereocilia. |
In vitro F-actin bundling assay with purified protein, overexpression and knockdown in cultured cells with morphological readout, fractionation identifying MISP in highly insoluble scaffold fraction |
Genes to cells : devoted to molecular & cellular mechanisms |
High |
24475924
|
| 2018 |
MISP functions downstream of the ERM family member ezrin and upstream of NuMA in the spindle orientation pathway. SLK/LOK-activated (phosphorylated) ezrin competes with MISP for actin-binding sites at the cell cortex, limiting cortical MISP levels. Excessive MISP accumulation disrupts crescent-like NuMA polarization at the cortex and reduces astral microtubule dynamics. MISP directly interacts with ezrin. |
Co-immunoprecipitation (MISP–ezrin interaction), siRNA epistasis experiments (SLK/LOK, ezrin, MISP), live-cell imaging of NuMA localization and astral microtubule dynamics, cortical fractionation |
Journal of cell science |
High |
29669740
|
| 2018 |
MISP interacts with the scaffolding protein IQGAP1, and through IQGAP1 binds the active (GTP-bound) form of Cdc42. MISP depletion increases IQGAP1 cortical accumulation and decreases Cdc42 activity. IQGAP1 overexpression rescues MISP-depletion phenotypes (spindle misorientation, loss of astral microtubules, prolonged mitosis) and restores active Cdc42 levels, placing IQGAP1 downstream of MISP. IQGAP1 also acts downstream of MISP in controlling p150(glued) localization. |
Co-immunoprecipitation (MISP–IQGAP1, IQGAP1–Cdc42), siRNA depletion epistasis, active-Cdc42 pull-down assay, IQGAP1 overexpression rescue experiments, immunofluorescence of p150(glued) localization |
Scientific reports |
High |
29679050
|
| 2021 |
Phosphorylation of MISP at S394, S395, and S400 increases actin-bundling activity (but not actin-binding activity), inducing stress fiber formation in interphase cells. Mitotic phosphorylation at S376, S471, and S541 suppresses actin-binding activity. Thus, cell-cycle-dependent phosphorylation differentially regulates MISP actin-binding versus bundling activities. |
Site-directed mutagenesis of phosphorylation sites, in vitro actin-binding and bundling assays, overexpression of phosphomutants in cells with morphological readout |
Biochemical and biophysical research communications |
High |
34023777
|
| 2022 |
MISP localizes specifically to the rootlet end (basal, pointed-end side) of microvillar actin core bundles in transporting epithelia. Purified MISP exhibits potent F-actin bundling activity in vitro and promotes rootlet elongation in cells. MISP-bundled filaments recruit fimbrin, which further elongates and stabilizes bundles. Ezrin prevents MISP from decorating the membrane-wrapped distal end of the core bundle, confining MISP to the rootlet. |
Immunofluorescence/live imaging for localization, in vitro actin bundling assay with purified protein, siRNA/CRISPR KO with microvillar phenotype readout (rootlet length), co-sedimentation assays, ezrin loss-of-function experiments |
Cell reports |
High |
35443169
|
| 2023 |
MISP downregulation by M2 macrophage-derived extracellular vesicles promotes IQGAP1 nuclear translocation and activates STAT3 phosphorylation in hepatocellular carcinoma cells, leading to upregulation of PD-L1 and immune escape. MISP, IQGAP1, and STAT3 interact in a complex as shown by co-immunoprecipitation. MISP negatively correlates with IQGAP1/PD-L1 expression. |
Co-immunoprecipitation (MISP–IQGAP1–STAT3 complex), MISP/IQGAP1 overexpression experiments, flow cytometry of CD8+ T cells, ELISA for cytokines, in vivo nude mouse xenograft |
International immunopharmacology |
Medium |
37633233
|
| 2023 |
In intrahepatic cholangiocarcinoma cells, MISP localizes to adherens junctions and suppresses E-cadherin dimerization. PLK1 phosphorylates MISP (confirmed as a PLK1 substrate in this context) and, together with MISP, disrupts adherens junctions to promote lymphatic invasion and cell motility. |
siRNA knockdown of PLK1 or MISP with trans-lymphatic endothelial migration and wound healing assays, immunofluorescence of focal adhesions and adherens junctions, in vivo tumorigenesis assay |
Cancer gene therapy |
Medium |
38057358
|
| 2024 |
MISP directly binds the SARAH domain of MST1/2 kinases, inhibiting their homodimerization and autophosphorylation, thereby sustaining YAP activation (Hippo pathway inhibition). YAP activation in turn increases SLC7A11 expression to protect cells from ferroptosis. A MISP-R390/391A mutant that disrupts MISP–MST1/2 binding abolishes this effect. YAP also transcriptionally activates MISP, creating a positive feedback loop. |
Co-immunoprecipitation (MISP–MST1/2), site-directed mutagenesis (R390/391A), in vitro kinase/autophosphorylation assay, siRNA knockdown with ferroptosis sensitivity readout, Western blot for Hippo pathway components, in vivo xenograft |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
High |
40019375
|
| 2024 |
MISP preferentially binds ADP-actin (aged/pointed-end-enriched) filaments over ADP-Pi-actin filaments, and in vitro TIRF assays show MISP binds at or near the pointed ends of growing actin filaments. In solution, MISP assembles parallel bundles of uniform polarity, whereas substrate-attached MISP can bundle filaments in both parallel and antiparallel configurations. Microvillar rootlets are decorated with cofilin (indicating high ADP-actin content), consistent with MISP's nucleotide-state preference driving its rootlet localization. |
In vitro TIRF microscopy with purified MISP and differentially nucleotide-loaded actin filaments, immunostaining of native intestinal tissue for cofilin, in vitro bundling assays in solution vs. substrate-attached conditions |
The Journal of biological chemistry |
High |
37205433 38588808
|
| 2024 |
MISP promotes nuclear accumulation of β-catenin, thereby activating the Wnt/β-catenin signaling pathway in pancreatic cancer cells. Fisetin suppresses MISP expression by downregulating the transcription factor MYB, identifying MYB as a transcriptional activator of MISP. |
Overexpression/knockdown of MISP with Western blot for β-catenin nuclear localization, in vitro proliferation assays, in vivo xenograft, drug screening library |
Biochimica et biophysica acta. Molecular basis of disease |
Medium |
39278512
|
| 2024 |
MISP forms a complex with Opa Interacting Protein 5 (OIP5) in the cytoplasm, and MISP influences OIP5 expression in a unidirectional manner. MISP also increases phosphorylated STAT3 levels via the JAK2-STAT3 signaling pathway in colorectal cancer cells. |
Co-immunoprecipitation (MISP–OIP5 complex), Western blot for pSTAT3, MISP-deficient mouse model (AOM/DSS colitis-induced tumors), siRNA knockdown with cell proliferation readout |
International journal of molecular sciences |
Medium |
38474305
|
| 2025 |
MISP directly interacts with MST1 (co-immunoprecipitation confirmed), inhibiting Hippo signaling and leading to increased YAP, TAZ, and CYR61 expression and decreased MST1 and phospho-YAP levels in lung adenocarcinoma cells. |
Co-immunoprecipitation (MISP–MST1), Western blot for Hippo pathway components, overexpression/knockdown with in vitro and in vivo proliferation and migration assays |
Discover oncology |
Medium |
41249743
|
| 2022 |
MISP-deficient mice show exacerbated DSS-induced colitis, with decreased intestinal epithelial cell proliferation and significantly reduced Tgfb1 (TGF-β1) anti-inflammatory cytokine expression in the colon, indicating MISP supports colon recovery from inflammation partly through TGF-β1 signaling. |
MISP-knockout mouse model (DSS colitis), RT-qPCR for Tgfb1 and other cytokines, histological assessment of crypt morphology, Ki67 proliferation staining |
The Journal of veterinary medical science |
Medium |
36596561
|