| 2003 |
IIp45 (MIIP) protein binds directly to IGFBP-2 through the thyroglobulin-RGD region of the C terminus of IGFBP-2, as identified by yeast two-hybrid screen, and inhibits IGFBP-2-stimulated glioma cell invasion in vitro and in xenograft models. IIp45 consistently inhibited expression of invasion-associated genes including NFκB and its downstream target ICAM-1. |
Yeast two-hybrid screen, functional invasion assays (in vitro and xenograft), gene expression profiling |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
14617774
|
| 2009 |
IIp45/MIIP physically interacts with HDAC6 (requiring both catalytic domains of HDAC6 for binding), inhibits HDAC6 enzymatic activity, reduces HDAC6 protein stability, increases acetylated α-tubulin levels, and thereby inhibits cell migration. Knockdown of HDAC6 reversed the increased migration caused by MIIP siRNA knockdown. |
Yeast two-hybrid, GST pulldown, co-immunoprecipitation, HDAC activity assay, protein turnover assay, siRNA epistasis |
The Journal of biological chemistry |
High |
20008322
|
| 2010 |
MIIP interacts directly with Cdc20 and inhibits APC/C-mediated degradation of cyclin B1, thereby attenuating mitotic transition and increasing mitotic catastrophe. This mechanism contributes to inhibition of glioma development in a mouse model. |
Co-immunoprecipitation, in vitro interaction assay, mouse glial-specific model, colony formation and cell growth assays, siRNA knockdown |
Oncogene |
Medium |
20418911
|
| 2005 |
A tumor-specific alternatively spliced isoform of IIp45 (IIp45S), resulting from exclusion of exon 7 and encoding a frameshifted C-terminus, is expressed in 60% of GBM tissue samples and 100% of GBM cell lines but not in normal organs. The IIp45S protein is undetectable despite mRNA expression because it is rapidly degraded by the ubiquitin-proteasome mechanism. |
RT-PCR, sequencing, proteasome inhibitor experiments, western blot |
Cancer research |
Medium |
15867349
|
| 2016 |
MIIP attenuates Rac1 signaling in endometrial cancer by competing with Rac1-GTP for binding to the p21-binding domain of PAK1. MIIP and PAK1 bind each other through a C-terminal polyproline domain of MIIP, and deletion of this PAK1-binding domain reduces MIIP's cell migration-inhibiting activity. Elevated MIIP expression reduces lamellipodia formation. |
Co-immunoprecipitation, Rac1 activity assay, serial deletion constructs, immunofluorescence (F-actin), transwell migration assay |
Journal of hematology & oncology |
Medium |
27760566
|
| 2016 |
MIIP haploinsufficiency inhibits topoisomerase II (Topo II) activity and induces chromosomal missegregation, and also alters stability of APC/CCdc20 downstream proteins securin and cyclin B1, thereby acting as a chromosomal instability suppressor in colorectal cancer. |
Zinc finger nuclease-mediated gene deletion (haploinsufficiency), spectral karyotyping, topoisomerase II activity assay, western blot, in vivo xenograft |
The Journal of pathology |
Medium |
27741356
|
| 2016 |
MIIP overexpression reduces steady-state EGFR protein levels in lung cancer cells by accelerating EGFR protein turnover through both proteasomal degradation in the endoplasmic reticulum and lysosomal degradation after endocytic trafficking, leading to inhibition of downstream Ras/MEK signaling and cell proliferation. |
Pulse-chase with 35S-methionine, proteasome and lysosome inhibitor experiments, western blot, overexpression/knockdown, downstream signaling assays |
Oncotarget |
Medium |
26824318
|
| 2017 |
EGF stimulation induces PKCε-dependent phosphorylation of MIIP at Ser303. This phosphorylation promotes MIIP interaction with RelA/p65 in the nucleus, where MIIP prevents HDAC6-mediated deacetylation of RelA, thereby enhancing RelA transcriptional activity and facilitating tumor metastasis. PP1 phosphatase mediates dephosphorylation of MIIP-S303. |
Phosphorylation assays, co-immunoprecipitation, nuclear fractionation, PKCε kinase assay, PP1 phosphatase assay, loss-of-function and gain-of-function studies |
Nature communications |
High |
29038521
|
| 2018 |
MIIP suppresses HDAC6 deacetylase activity to promote acetylation and subsequent degradation of HIF-1α, thereby impairing HIF-1α accumulation in pancreatic cancer cells. Conversely, HIF-1α indirectly downregulates MIIP at the post-transcriptional level by activating transcription of miR-646, which targets MIIP mRNA coding sequence and impairs its stability. |
ChIP, luciferase reporter assay, miRNA array, overexpression/knockdown, HDAC activity assay, co-immunoprecipitation, xenograft models |
Oncogene |
Medium |
29343850
|
| 2019 |
MIIP interacts with PP1α via its C-terminal part and facilitates PP1-mediated AKT dephosphorylation, thereby inhibiting AKT-mTOR signaling and prostate cancer cell growth. A C-terminal deletion mutant of MIIP (MIIPΔC) that cannot interact with PP1α loses this inhibitory function, and silencing PP1α reverses MIIP's inhibitory effect on AKT phosphorylation. |
Co-immunoprecipitation, immunofluorescence co-localization, western blot, deletion mutagenesis, siRNA knockdown, xenograft model |
Cell communication and signaling : CCS |
Medium |
31092266
|
| 2021 |
MIIP promotes HSP90 acetylation and impairs its chaperone function toward HIF-2α in clear cell renal cell carcinoma, leading to RACK1 binding HIF-2α and causing its ubiquitination and proteasomal degradation, consequently decreasing transcription of the HIF-2α target CYR61 and inhibiting proliferation and angiogenesis. |
Co-immunoprecipitation, ubiquitination assay, RNA-sequencing, overexpression/knockdown, xenograft model, western blot, ELISA |
Cancer biology & medicine |
Medium |
34931765
|
| 2022 |
MIIP directly interacts with integrin β3 (ITGB3) through its RGD motif, suppresses ITGB3 downstream signaling, elevates ubiquitin-mediated β-catenin degradation, reduces VEGFA production, and inhibits EMT, thereby suppressing angiogenesis and tumorigenesis in triple-negative breast cancer. |
Co-immunoprecipitation, RGD-mutant functional assays, ubiquitination assay, in vitro and in vivo functional assays |
Cell death & disease |
Medium |
36130933
|
| 2024 |
MIIP interacts with the lipid mobilization factor AZGP1 and regulates its N-glycosylation by interfering with its association with the glycosyltransferase STT3A. MIIP downregulation promotes STT3A-mediated N-glycosylation and oversecretion of AZGP1, which then induces adipocyte browning and lipolysis through the cAMP-PKA pathway in colorectal cancer. |
Co-immunoprecipitation, glycosylation assays, in vitro co-culture model, in vivo allograft model, western blot |
Cell & bioscience |
Medium |
38245780
|
| 2024 |
MIIP localizes between microtubule triplets at the A-C linker of centrioles, forming a complex with CCDC77 and WDR67. Depletion of A-C linker components including MIIP disrupts microtubule triplet cohesion, causing breakage at the proximal end of centrioles. The A-C linker (including MIIP) also plays a role in centriole duplication through torus regulation. |
Ultrastructure expansion microscopy, protein depletion (siRNA/knockdown), co-localization studies |
bioRxivpreprint |
Low |
bio_10.1101_2024.10.04.616628
|