| 1998 |
MSP58 (MCRS1) physically interacts with nucleolar protein p120; the interaction requires the coiled-coil domain in the N-terminal region of p120 and the C-terminal region of MSP58, as shown by yeast two-hybrid, recombinant co-expression in Sf9 cells, and deletion mutagenesis. MSP58 localizes to microspherules in the nucleolus, and overexpression causes irregular nucleolar enlargement in COS-7 cells. |
Yeast two-hybrid, recombinant protein co-expression in insect Sf9 cells, deletion mutagenesis, immunofluorescence |
European journal of biochemistry |
High |
9654073
|
| 2004 |
MCRS2 (splice variant of MCRS1/p78) interacts with the telomerase-inhibitory protein LPTS/PinX1 in vitro and in vivo, co-localizes with LPTS/PinX1 in cells, inhibits telomerase activity in vitro, and its long-term overexpression progressively shortens telomeres in SMMC-7721 cells. MCRS2 expression is cell-cycle dependent, accumulating in early S phase. |
Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, immunofluorescence co-localization, telomerase activity assay, telomere length measurement |
Biochemical and biophysical research communications |
High |
15044100
|
| 2005 |
The PTEN C-terminal domain physically interacts with the forkhead-associated (FHA) domain of MSP58 (MCRS1), requiring PTEN Thr-366. This interaction suppresses MSP58-driven cellular transformation, as PTEN(T366A) mutant fails to suppress MSP58-induced foci formation, while catalytically inactive PTEN (G129R) retains suppressive activity, demonstrating the C-terminal interaction (not phosphatase activity) is responsible. |
Co-immunoprecipitation, focus-formation assay in Pten-/- MEFs, point-mutant analysis (T366A, G129R) |
Proceedings of the National Academy of Sciences of the United States of America |
High |
15659546
|
| 2005 |
MSP58 (MCRS1) interacts with the bHLH transcription factor STRA13 through the basic domain of STRA13 and the FHA domain of MSP58; this interaction is modulated by STRA13 phosphorylation status. Complex formation protects both proteins from proteasome-mediated degradation, extending their half-lives. MSP58 and STRA13 synergistically repress STRA13 promoter-driven transcription and both proteins accumulate during S phase. |
Yeast two-hybrid, co-immunoprecipitation, phospho-peptide mapping, proteasome inhibitor experiments, luciferase reporter assay, cell-cycle expression analysis |
Cellular and molecular life sciences : CMLS |
High |
15719173
|
| 2006 |
p78/MCRS1 associates with centrosomal proteins Nde1 and Su48; the FHA domain of p78 is required for these interactions and for centrosomal localization. A fraction of p78 localizes to the centrosome (in addition to the nucleus). The Nde1-p78 interaction is regulated by phosphorylation of Nde1. siRNA knockdown of p78 causes cell death and a modest mitotic delay. |
Yeast two-hybrid, co-immunoprecipitation, immunofluorescence (centrosome localization), domain mapping, siRNA knockdown with viability and cell-cycle assays |
Oncogene |
High |
16547491
|
| 2006 |
DIPA (delta-interacting protein A) physically associates with p78/MCRS1/MSP58 as shown by co-immunoprecipitation; the structural regions mediating the interaction were identified. DIPA co-localizes predominantly with p78 in the nucleus, and DIPA acts as a repressor of gene transcription, an activity enhanced by p78. |
Co-immunoprecipitation, domain mapping, immunofluorescence co-localization, transcriptional reporter assay |
Experimental and molecular pathology |
Medium |
17014843
|
| 2006 |
NDRG2 interacts with MSP58 (MCRS1); the FHA domain of MSP58 is essential for this interaction. NDRG2 co-localizes with MSP58 in the nucleus of HeLa cells during cell stress. Modulation of NDRG2 levels influences cell cycle progression together with MSP58. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, immunofluorescence co-localization, cell cycle analysis |
Biochemical and biophysical research communications |
Medium |
17109818
|
| 2009 |
MCRS2 (isoform of MCRS1) directly interacts with the CNC-bZIP transcription factor Nrf1; the interaction domains were mapped to residues 354–447 of Nrf1 and residues 314–475 of MCRS2. MCRS2 co-localizes with Nrf1 in the nucleus and represses Nrf1-mediated transcriptional activation in reporter assays. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, immunofluorescence, luciferase reporter assay |
BMC cell biology |
High |
19187526
|
| 2010 |
Drosophila MCRS2 (ortholog of human MCRS1/MCRS2) co-purifies with RNA polymerase II complexes, localizes to the 5' ends of genes, and is required for optimal recruitment of RNAP II to promoter regions of cyclin genes and for normal cyclin gene expression levels. |
Co-purification/co-IP with RNAP II, chromatin immunoprecipitation (ChIP), RNA expression analysis, genetic knockdown |
Molecular and cellular biology |
High |
20679484
|
| 2012 |
MSP58 (MCRS1) forms a ternary complex with p53 and BRG1 (SWI/SNF subunit) on the p21 promoter to activate p21 transcription. MSP58 also activates the DNA damage response and p53/p21 signaling pathways. MSP58-induced senescence strictly requires functional p53; cells with p53 knockdown or mutant p53 bypass MSP58-induced senescence. |
Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (ternary complex), shRNA knockdown of p53, ectopic overexpression, senescence assays (β-galactosidase), western blot |
The Journal of biological chemistry |
High |
22563078
|
| 2012 |
EDD (UBR5), a HECT-domain ubiquitin E3 ligase, directly interacts with MSP58 (MCRS1) in vitro and in vivo. EDD depletion increases MSP58 protein levels and extends its half-life. MSP58 is ubiquitinated and degraded via the ubiquitin-proteasome pathway. Knockdown of either MSP58 or EDD alters cyclin B, D, and E levels and cell cycle progression. |
Co-immunoprecipitation, in vitro binding assay, proteasome inhibitor (MG132) treatment, ubiquitination assay, siRNA knockdown with western blot and cell cycle analysis |
Biochimica et biophysica acta |
High |
23069210
|
| 2015 |
MCRS1 is an essential link between Rheb and mTORC1 activation by amino acids (AAs). In an AA-dependent manner, MCRS1 maintains Rheb at lysosome surfaces. MCRS1 depletion (siRNA or Cre/Lox in MEFs) reduces mTORC1 activity, promotes Rheb–TSC2 interaction (rendering Rheb inactive), and delocalizes Rheb from lysosomes to recycling endocytic vesicles. |
siRNA knockdown, inducible Cre/Lox knockout in MEFs, co-immunoprecipitation, immunofluorescence (lysosomal localization of Rheb), mTORC1 activity assays, amino acid stimulation/deprivation |
Developmental cell |
High |
25816988
|
| 2015 |
BAP1, a nuclear de-ubiquitinating enzyme, binds MCRS1 and stabilizes it by removing ubiquitin chains (de-ubiquitination), thereby preventing proteasomal degradation of MCRS1. BAP1 contributes to chromosome stability partially through MCRS1. MCRS1 is a component of centrosomal proteins and plays an essential role in spindle assembly. |
Co-immunoprecipitation, de-ubiquitination assay, BAP1 knockdown/knockout with MCRS1 stability measurement, chromosome instability assays |
Cancer letters |
High |
26300492
|
| 2015 |
MSP58 (MCRS1) contains two nuclear localization signals (NLS1: residues 32–56; NLS2: residues 113–123) and a bipartite nucleolar localization signal within NLS1 (residues 44–56). MSP58 binds importin α1 and α6, indicating receptor-mediated nuclear import. Both nuclear and nucleolar localization are required for MSP58-mediated transcriptional regulation of p21 and ribosomal RNA genes. |
Deletion/mutation analysis of NLS/NoLS, yeast two-hybrid, GST pull-down, co-immunoprecipitation with importins, reporter assays, immunofluorescence |
Journal of biomedical science |
High |
25981436
|
| 2016 |
MCRS1 localizes to centriolar satellites and is required for dynein-dependent cargo transport to the centrosome. MCRS1 knockdown disperses centriolar satellites. MCRS1 plays a positive role in ciliogenesis initiation, possibly through interaction with TTBK2. Zebrafish mcrs1 mutants show brain/eye size reduction due to apoptosis, defective retinal layering, melanosome aggregation defects, and reduced ciliogenesis — phenotypes resembling dynein mutants. Additionally, MCRS1 directly associates with cytoplasmic dynein. |
siRNA knockdown, immunofluorescence (centriolar satellite localization), zebrafish mcrs1 mutant phenotype analysis, co-immunoprecipitation with dynein components, ciliogenesis assays |
Scientific reports |
High |
27263857
|
| 2016 |
Aurora-A kinase phosphorylates MCRS1 on Ser35/36 during mitosis. This phosphorylation does not affect MCRS1 localization to chromosomal MTs or K-fiber minus-ends, but regulates MCRS1 activity in mitosis, particularly in tuning kinetochore fiber (K-fiber) minus-end dynamics. |
In vitro kinase assay, phospho-site mutagenesis, immunofluorescence, siRNA-based functional assays in mitosis |
Cell cycle (Georgetown, Tex.) |
Medium |
27192185
|
| 2016 |
MCRS1 (MSP58) directly interacts with RINT-1 in vitro and in vivo; both proteins co-localize with UBF in the nucleolus. Overexpression of either MSP58 or RINT-1 decreases rRNA expression and rDNA promoter activity, while co-expression produces a greater decrease. Both MSP58 and RINT-1 associate with the rDNA promoter as shown by ChIP. |
Yeast two-hybrid, in vitro binding, co-immunoprecipitation, immunofluorescence co-localization, rRNA expression assays, rDNA promoter reporter assay, chromatin immunoprecipitation (ChIP) |
Biochemical and biophysical research communications |
High |
27530925
|
| 2019 |
Mps1 kinase binds and phosphorylates MCRS1, enabling KIF2A localization to the minus end of spindle microtubules, thereby regulating chromosome alignment. MCRS1 controls the dynamics of the minus end of kinetochore microtubules. |
Co-immunoprecipitation (Mps1–MCRS1 binding), in vitro kinase assay (phosphorylation), immunofluorescence (KIF2A localization), siRNA/inhibitor-based functional assays (chromosome alignment) |
Molecular biology of the cell |
High |
30785839
|
| 2019 |
MCRS1 physically interacts with Pkmyt1 (a WEE1-family kinase) in vitro and the two proteins co-localize in the cytoplasm. Overexpression of MCRS1 inhibits growth, invasion and migration of gastric cancer cells and suppresses Pkmyt1 expression, while downregulation of MCRS1 promotes these phenotypes; inhibition of WEE1/Pkmyt1 with MK1775 rescues the MCRS1-knockdown phenotype. |
Co-immunoprecipitation, immunofluorescence co-localization, overexpression/knockdown cell assays, kinase inhibitor (MK1775) epistasis |
Cellular signalling |
Medium |
30953699
|
| 2020 |
MCRS1 is essential for epiblast development in early murine embryogenesis. Mcrs1 mutant embryos show normal blastocyst morphology but fail to form an inner cell mass colony in outgrowth assays; trophoblast and primitive endoderm are properly specified, but the epiblast lineage is specifically compromised with severely reduced cell number. Global H4 acetylation and apoptosis are normal in mutant blastocysts. |
Conditional Mcrs1 knockout mouse, outgrowth assays, lineage marker immunostaining, histone H4 acetylation analysis, apoptosis assay |
Reproduction (Cambridge, England) |
High |
31671403
|
| 2020 |
Mcrs1 binds to the Six1 transcription factor (confirmed in cultured cells and embryonic ectoderm) and reduces Six1-Eya1 transcriptional activation. Knockdown of Mcrs1 in Xenopus embryos causes expansion of neural plate gene domains, reduction of pre-migratory neural crest genes (foxd3, sox9), and pleiotropic effects on cranial placode genes. Double knockdown and rescue experiments establish a functional interaction between Mcrs1 and Six1 required for otic vesicle development. |
Co-immunoprecipitation (Mcrs1–Six1 binding), transcriptional reporter assay (Six1-Eya1 activity), antisense morpholino knockdown in Xenopus, rescue experiments, in situ hybridization for lineage markers |
Developmental biology |
High |
32891623
|
| 2022 |
Mcrs1 localizes to spindle poles and chromosomes of mouse oocytes during meiosis I. Depletion of Mcrs1 alters HDAC2-mediated H4K16ac, H3K4me2, and H3K9me2 chromatin modifications in NSN-type oocytes, reduces CDK1 activity and cyclin B1 accumulation causing G2/M transition delay, and results in abnormal spindle assembly due to reduced Aurora kinase (Aurka, Aurkc) and Kif2A activities. |
siRNA knockdown in mouse oocytes, immunofluorescence (spindle localization), histone modification immunostaining, CDK1 activity assay, western blot (cyclin B1), Aurora kinase and Kif2A activity assays |
EMBO reports |
High |
36951681
|
| 2022 |
Silencing MCRS1 increases the proportion of open (versus closed) microtubule minus-end morphologies in metaphase HeLa cell spindles as measured by large-scale electron tomography, demonstrating that MCRS1 stabilizes MT minus ends and modulates their structural heterogeneity. |
siRNA knockdown of MCRS1, large-scale electron tomography of 3D-reconstructed metaphase spindles in HeLa cells |
Molecular biology of the cell |
High |
36350698
|
| 2024 |
MCRS1 interacts with the transcription factor YY1 and coordinately increases chromatin accessibility and expression of MHC-I genes, thereby augmenting antigen presentation in pancreatic cancer cells and sensitizing them to T cell-mediated killing and anti-PD-1 therapy. |
CRISPR activation screen, co-immunoprecipitation (MCRS1–YY1), ATAC-seq/chromatin accessibility assay, MHC-I expression (flow cytometry/western blot), T cell killing assay, in vivo tumor model with anti-PD-1 |
The Journal of experimental medicine |
High |
39545935
|
| 2025 |
CRISPRi knockdown of MCRS1 in hiPSC-derived neural progenitors drives precocious neural commitment. MCRS1 represses ZEB1 expression, positioning MCRS1 as a brake on premature neurodevelopment. Gene regulatory network inference identified MCRS1 as a key upstream regulator of the ZEB1-mediated neural differentiation axis. |
Pooled CRISPRi screen with single-cell multiomics (scRNA-seq + ATAC-seq), gene regulatory network (GRN) inference, validation in hiPSC-derived neurons |
bioRxivpreprint |
Medium |
|
| 2024 |
MCRS1 (Mcrs1) acts as a bona fide SIX1 co-factor that represses SIX1+EYA transcriptional activity in mouse. MCRS1 can translocate EYA to the nucleus indirectly (in contrast to SOBP which does so directly). MCRS1 and SOBP are co-expressed with SIX1 in the oral domain of the mandibular arch. |
Co-immunoprecipitation (MCRS1–SIX1 binding), transcriptional reporter assay (SIX1+EYA activity), nuclear translocation assay, immunofluorescence co-localization in mouse tissue |
bioRxivpreprint |
Medium |
|