| 1998 |
MOB1 (yeast) physically binds DBF2 in vivo and in vitro in the absence of other yeast proteins; this interaction is required for the late mitotic function of DBF2, as temperature-sensitive MOB1 mutants that cannot bind DBF2 fail to execute the telophase/G1 transition. Overexpression of MOB1 suppresses lethality of dbf2Δ dbf20Δ double deletion, indicating DBF2 acts through MOB1. |
Two-hybrid screen, co-immunoprecipitation, in vitro binding, genetic suppression analysis |
Molecular and cellular biology |
High |
9528782
|
| 1998 |
Yeast MOB1 is a phosphoprotein in vivo and a substrate for the Mps1p kinase in vitro; loss-of-function mob1 alleles cause late nuclear division arrest, and MOB1 shows genetic interactions with LTE1, CDC5, and CDC15, placing it in the mitotic exit pathway. |
Two-hybrid screen, in vitro kinase assay, conditional allele analysis, genetic interaction |
Molecular biology of the cell |
High |
9436989
|
| 2001 |
Cdc15 kinase activates the Dbf2-Mob1 complex in vitro only when Dbf2 is bound to Mob1; Cdc15 phosphorylates conserved sites Ser-374 and Thr-544 on Dbf2, and Mob1 enables Cdc15 to phosphorylate these critical sites. Dbf2 kinase activity in vivo depends on Tem1, Cdc15, and Mob1. |
In vitro kinase reconstitution, site-directed mutagenesis, in vivo activity assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
11404483
|
| 2001 |
Genetic epistasis in budding yeast places Tem1 upstream of Cdc15, which functions upstream of Mob1 and Dbf2 in the mitotic exit network; Dbf2 kinase activity and actin ring formation at the bud neck are both controlled by the same MEN components including Mob1. |
Genetic epistasis, Dbf2 kinase activity assays, actin ring visualization |
Current biology : CB |
High |
11378390
|
| 2001 |
Mammalian MOB1 (mMOB1) associates with striatin/SG2NA-PP2A complexes; PP2A dephosphorylates mMOB1 since PP2A inhibition with okadaic acid induces serine phosphorylation of PP2A-associated mMOB1. mMOB1 localizes adjacent to the nuclear membrane in murine fibroblasts. |
Co-immunoprecipitation, pharmacological PP2A inhibition, indirect immunofluorescence, mass spectrometry identification |
The Journal of biological chemistry |
Medium |
11319234
|
| 2001 |
Dbf2 and Mob1 (yeast) localize to spindle pole bodies in anaphase and then relocalize to the bud neck just prior to actin ring assembly; bud-neck localization but not SPB localization of Dbf2 is inhibited by the Bub2 spindle checkpoint, and neck localization of both Dbf2 and Mob1 depends on Cdc14 activity. |
Fluorescence microscopy of tagged proteins, genetic analysis with checkpoint and cdc14 mutants |
Genes & genetic systems |
Medium |
11434459
|
| 2003 |
Crystal structure of human MOB1A reveals a four-helix bundle stabilized by a bound zinc atom; the N-terminal helix and adjacent elements form an evolutionarily conserved surface with strong negative electrostatic potential that is targeted by temperature-sensitive yeast MOB1 alleles, suggesting this surface mediates electrostatic interactions with basic regions of kinase partners. |
X-ray crystallography |
Structure (London, England : 1993) |
High |
12962634
|
| 2004 |
NMR solution structure of Xenopus Mob1 shows a four-helix bundle with a zinc-binding site; chemical shift perturbations upon addition of a peptide from the N-terminal regulatory domain of NDR kinase map the NDR-binding interface to the conserved acidic surface of Mob1, confirming this surface mediates kinase interaction. |
Heteronuclear multidimensional NMR, chemical shift perturbation mapping |
Journal of molecular biology |
High |
15001360
|
| 2005 |
The Dbf2-Mob1 kinase complex preferentially phosphorylates substrates containing an RXXS motif (serine over threonine required; arginine at -3 position essential and cannot be substituted by lysine), as determined by peptide library selection and proteome chip screening. |
Peptide library selection, phosphorylation of optimal peptide variants, proteome microarray |
BMC biochemistry |
High |
16242037
|
| 2006 |
Human MOB1 activates LATS1 kinase when membrane-targeted (but not when merely co-expressed); activation requires intact phosphorylation sites in LATS1's activation segment and hydrophobic motif, and occurs within minutes of membrane association. A conserved MOB1-binding motif within LATS1 was identified. |
Co-expression with membrane-targeting constructs, kinase activity assays, site-directed mutagenesis |
Biochemical and biophysical research communications |
Medium |
16674920
|
| 2006 |
Crystal structure of S. cerevisiae Mob1 (full-length, 2.0 Å) reveals N-terminal structural elements (helix H0, strand S0, strand S-1); H0 mediates intermolecular homodimerization and S0 binds intramolecularly across the Dbf2-binding site. In vivo functional analysis shows Mob1 mutants targeting H0 or its binding site are biologically compromised. |
X-ray crystallography, in vivo yeast functional analysis |
Journal of molecular biology |
High |
16934835
|
| 2008 |
MST2 phosphorylates MOB1 at Thr74 in vitro; phosphorylation at Thr74 (but not Thr181) is essential for the formation of a MOB1-MST2-NDR1 scaffold complex and for full NDR1 activation. MOB1-T74A fails to enhance its interaction with NDR1 upon okadaic acid treatment. Knockdown of MOB1 or MST2 abolishes NDR1 activation in cells. |
In vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, RNAi knockdown, NDR1 kinase activity assay |
Oncogene |
High |
18362890
|
| 2009 |
The Dbf2-Mob1 kinase complex directly phosphorylates Cdc14 phosphatase on serine and threonine residues adjacent to its nuclear localization signal (NLS), thereby abrogating NLS activity and promoting Cdc14 relocalization from the nucleolus to the cytoplasm during mitotic exit. |
In vitro kinase assay, mass spectrometry phosphorylation site mapping, nuclear localization assays |
The Journal of cell biology |
High |
19221193
|
| 2009 |
Human Mob1 localizes to spindle poles and kinetochores in early mitosis and to the spindle midzone during cytokinesis; chromosomal passenger complex (CPC) disruption abolishes Mob1 recruitment to kinetochores (but not spindle poles), while Plk1 depletion eliminates spindle-pole Mob1. Mob1 depletion delays CPC and MKLP2 relocalization to the spindle midzone in early anaphase. |
Immunofluorescence, RNAi depletion, live-cell imaging |
Molecular biology of the cell |
Medium |
19955215
|
| 2012 |
Human Mob1A and Mob1B are required for cytokinetic abscission; RNAi depletion causes abscission failure due to hyper-stabilization of microtubules in the midbody region. Mob1 depletion also increases cell motility and induces prolonged centriole separation in G1; conversely, Mob1A or Mob1B overexpression prevents centrosome splitting. |
RNAi depletion, microtubule stability assay, live-cell imaging, cytokinesis assay |
Journal of cell science |
Medium |
22454515
|
| 2013 |
The RING E3 ubiquitin ligase praja2 ubiquitylates and targets MOB1 for proteasomal degradation; this degradation attenuates LATS/NDR kinase activity and the Hippo tumor-suppressor cascade, sustaining glioblastoma growth in vivo. |
Co-immunoprecipitation, ubiquitylation assay, proteasome inhibition, in vivo tumor growth |
Nature communications |
High |
23652010
|
| 2015 |
Human MOB1 binds autophosphorylated docking motifs in active MST2, enabling MOB1 phosphorylation by MST2; phosphorylated MOB1 undergoes conformational activation and binds LATS1. Crystal structures of phospho-MST2-MOB1 and phospho-MOB1-LATS1 complexes reveal phosphorylation-dependent binding events. MOB1 mediates LATS1 activation through dynamic scaffolding and allosteric mechanisms. |
Biochemical binding assays, in vitro kinase assays, X-ray crystallography, functional epistasis |
Genes & development |
High |
26108669
|
| 2015 |
Mob1a/Mob1b double knockout in mouse liver causes hyperproliferation, hepatocyte dedifferentiation, enhanced epithelial-mesenchymal transition, and development of liver cancers; these phenotypes are strongly dependent on YAP1 and partially on TAZ and TGF-β2/3 signaling, placing MOB1A/B as the critical hub of Hippo signaling upstream of LATS-YAP1/TAZ. |
Conditional knockout mice, genetic epistasis (Yap1 rescue), drug screening, cell culture assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
26699479
|
| 2016 |
Crystal structure of full-length MOB1B reveals an autoinhibited conformation where the N-terminal Switch helix (stabilized by SN strand β-sheet formation) blocks the LATS1-binding surface. MST1/2-mediated phosphorylation of Thr12 and Thr35 structurally relieves autoinhibition via a 'pull-the-string' mechanism, enabling LATS1 binding. |
X-ray crystallography of full-length MOB1B, complex with LATS1 NTR, biochemical validation |
Scientific reports |
High |
27335147
|
| 2017 |
MOB1A phosphopeptide-binding specificity is highly complementary to MST1/2 substrate phosphorylation consensus; autophosphorylation of MST1/2 on multiple threonine residues provides several MOB1A-binding sites with varying affinities. Crystal structures of MOB1A with two MST1 phosphopeptides define the phosphopeptide-binding consensus. Phosphopeptide-binding is conserved in six of seven human MOB family members. |
Proteomics, peptide arrays, biochemical binding assays, X-ray crystallography, interaction proteomics |
Molecular & cellular proteomics : MCP |
High |
28373298
|
| 2017 |
MOB1 phosphorylation by upstream MST kinases differentially regulates its two protein interaction surfaces: phosphorylation promotes binding to MST via the phosphopeptide-binding surface while modulating LATS/NDR binding at a distinct surface. MOB1A also associates in a phosphorylation-dependent manner with PP6 phosphatase and Rho guanine exchange factor complexes (DOCK6-8) through mechanisms distinct from MST1/2 binding. |
Biochemical assays, biophysical binding measurements, mutagenesis, structural analysis, interaction proteomics |
Molecular & cellular proteomics : MCP |
High |
28373297
|
| 2017 |
MOB1/Warts (LATS) binding is essential for tumor suppression, tissue growth control, and development in Drosophila and human cells, while stable MOB1/Hippo (MST) binding is dispensable and MOB1/Trc (NDR) binding alone is insufficient. Crystal structure of the MOB1/NDR2 complex defines key residues for differential binding to Hippo core kinases. |
Crystal structure, mutagenesis, Drosophila genetic analysis, human cancer cell studies |
Nature communications |
High |
28947795
|
| 2019 |
Kindlin-2 (focal adhesion molecule) interacts with MOB1 and promotes its degradation by enhancing MOB1-praja2 (E3 ligase) interaction; this inhibits LATS1 phosphorylation and YAP phosphorylation, promoting YAP nuclear translocation. Kindlin-2 depletion activates Hippo/YAP signaling and alleviates renal fibrosis in vivo. |
Co-immunoprecipitation, ubiquitylation assay, MOB1 degradation assay, mouse knockout with UUO model |
Cell reports |
Medium |
31825843
|
| 2019 |
PR55α regulatory subunit of PP2A inhibits MOB1-triggered autoactivation of LATS1/2 kinases, thereby promoting YAP activation; PR55α also directly interacts with YAP. This identifies a PP2A-MOB1-LATS1/2 axis controlling YAP in pancreatic cancer cells. |
Co-immunoprecipitation, kinase activity assay, RNAi knockdown, anchorage-independent growth assay |
Oncogenesis |
Medium |
31659153
|
| 2018 |
MOB1 stability is regulated by the PTEN-GSK3β axis; GSK3β phosphorylates MOB1 on Ser146, targeting it for ubiquitin-proteasome degradation. PTEN knockdown (via PI3K-AKT) suppresses GSK3β and stabilizes MOB1 protein, promoting neurite outgrowth. |
In vitro kinase assay, site-directed mutagenesis, ubiquitin-proteasome assay, lentiviral in vivo silencing |
Cellular and molecular life sciences : CMLS |
Medium |
30069702
|
| 2020 |
The Legionella pneumophila effector kinase LegK7 uses MOB1A as both a substrate and an allosteric activator; MOB1A binding to the LegK7 kinase domain reorients the two kinase lobes into an ATP-binding-compatible closed conformation. The MOB1A N-terminal extension (NTE) serves as a docking site for downstream substrates (YAP1). Crystal structure of the LegK7-MOB1A complex was determined. |
X-ray crystallography, in vitro kinase assay, mutagenesis of interface residues, cell-based phosphorylation assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
32513747
|
| 2021 |
EGFR promotes tyrosine phosphorylation of MOB1 (a core Hippo component) and inactivates LATS1/2 independently of MST1/2, thereby activating YAP/TAZ in head and neck squamous cell carcinoma cells. |
Phosphorylation assays, kinase inhibition (erlotinib), RNAi and loss-of-function experiments, transcriptomic analysis |
Communications biology |
Medium |
34725466
|
| 2022 |
MOB1 is acetylated at Lys11 by acetyltransferase CBP and deacetylated by HDAC6; MOB1-K11 acetylation stabilizes MOB1 by reducing its binding to E3 ligase Praja2 and subsequent ubiquitination, and also increases MOB1 phosphorylation and activates LATS1. Oxidative stress promotes MOB1 acetylation by suppressing CBP degradation, independently of MST1/2 kinase activity. |
Co-immunoprecipitation, ubiquitylation assay, in vitro acetylation assay, site-directed mutagenesis (K11R), in vitro and in vivo tumor assays |
Nucleic acids research |
High |
35349706
|
| 2022 |
The lncRNA WEE2-AS1 (from CAF-derived exosomes) functions as a scaffold bridging MOB1A and E3 ligase praja2, leading to MOB1A ubiquitin-proteasome degradation, Hippo pathway inhibition, and increased YAP nuclear translocation in colorectal cancer cells. |
Co-immunoprecipitation, RNA-protein interaction assay, ubiquitylation assay, in vivo tumor model |
Cell death & disease |
Medium |
36123327
|
| 2010 |
Among all seven human MOB family members, only hMOB1A and hMOB1B interact with both LATS1 and LATS2 in vitro and in vivo; overexpression of hMOB1 in cancer cells activates LATS kinase activity and inhibits proliferation or causes apoptosis, with membrane-targeted hMOB1 producing stronger effects. |
Co-immunoprecipitation, in vitro binding, kinase activity assay, overexpression and shRNA knockdown in cancer cells |
International journal of cancer |
Medium |
19739119
|