Affinage

MST1

Hepatocyte growth factor-like protein · UniProt P26927

Length
711 aa
Mass
80.3 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MST1 (STK4) is a SARAH domain-containing serine/threonine kinase that functions as a central pro-apoptotic and growth-suppressive hub, integrating stress signals into the Hippo tumor-suppressor pathway, cell-death programs, and mitotic fidelity. MST1 is activated by autophosphorylation at Thr183 (enhanced by homodimerization and oxidized PRX-I oligomers) and inhibited by Akt (phospho-Thr120), mTORC2 (phospho-Ser438), FGFR4 (phospho-Tyr433), H-Ras/Erk-promoted MST1/MST2 heterodimerization, and SIRT7-mediated deacetylation-coupled ubiquitination (PMID:12223493, PMID:25843706, PMID:30903103, PMID:27238285, PMID:38288904). Upon activation, MST1 phosphorylates MOB1 to drive LATS1 activation and YAP suppression, FOXO1/3 to promote nuclear translocation and apoptosis, Bcl-xL Ser14 to release Bax, Aurora B to ensure kinetochore-microtubule attachment accuracy, PDX1 to trigger beta-cell dysfunction, Cx43 Ser255 to close endothelial hemichannels, and UNC5B Thr428 to execute dependence-receptor apoptosis; caspase cleavage removes C-terminal NES-containing sequences, enabling nuclear translocation where MST1 phosphorylates histone H2B to drive chromatin condensation (PMID:18328708, PMID:19221179, PMID:24813943, PMID:20171103, PMID:24633305, PMID:36164986, PMID:32929029, PMID:11517310). Combined Mst1/Mst2 loss in mouse liver abolishes YAP Ser127 phosphorylation and causes hepatocellular carcinoma, while MST1 also governs T-cell migration via MOB1-Dock8-Rac1 signaling, ciliogenesis through AURKA phosphorylation, and endothelial tip-cell polarity via ROS-FOXO1 signaling (PMID:19878874, PMID:22412158, PMID:25367221, PMID:30783090).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 High

    Establishing how MST1 reaches the nucleus during apoptosis: caspase cleavage removes C-terminal NES sequences, allowing the kinase domain to translocate to the nucleus and drive chromatin condensation — revealing a regulated nuclear entry mechanism.

    Evidence NES mutagenesis, leptomycin B treatment, subcellular fractionation, and staurosporine-induced apoptosis in mammalian cells

    PMID:11517310

    Open questions at the time
    • Identity of the nuclear chromatin substrates beyond condensation phenotype was not addressed
    • Whether caspase-independent nuclear entry occurs physiologically was unknown
  2. 2002 High

    Defining the activation mechanism: MST1 activates by intermolecular autophosphorylation at Thr183 enhanced by homodimerization, establishing that kinase activity — not caspase cleavage — is the primary requirement for JNK activation and apoptosis.

    Evidence In vitro kinase assay with site-directed mutagenesis of Thr183/Thr187/Thr177/Thr387 and cell-based apoptosis readouts

    PMID:12223493

    Open questions at the time
    • Structural basis for how dimerization promotes trans-autophosphorylation was not resolved
    • Upstream signals that trigger homodimerization in vivo were unknown
  3. 2006 High

    Linking MST1 to RASSF scaffold proteins: RASSF1A associates with MST1, co-localizes on microtubules, and is required for Fas-induced MST1 activation and apoptosis — connecting death-receptor signaling to MST1 via a tumor-suppressor scaffold.

    Evidence Co-IP, immunofluorescence, in vitro kinase assay, RNAi knockdown, Fas ligation apoptosis assay

    PMID:16510573

    Open questions at the time
    • Paradox of RASSF1A inhibiting MST1 in vitro but activating it in cells was mechanistically unresolved
    • Whether RASSF1A switches MST1 substrate specificity was not tested
  4. 2007 Medium

    Revealing reciprocal MST1–Akt inhibition: MST1 physically complexes with and inhibits Akt1 activity, establishing a bidirectional antagonism between survival and death kinases.

    Evidence Reciprocal Co-IP from endogenous proteins in lipid raft fractions, kinase activity assay, zebrafish epistasis

    PMID:17932490

    Open questions at the time
    • Single lab; independent confirmation in mammalian genetic models was lacking
    • Whether MST1 directly phosphorylates Akt or acts allosterically was not distinguished
  5. 2008 High

    Identifying MOB1 as the key MST1 substrate linking the Hippo cascade to LATS1 activation: MST1 phosphorylates MOB1, promoting its binding to LATS1 and LATS1 activation; non-phosphorylatable MOB1 accelerates proliferation.

    Evidence In vitro kinase assay, cell-based phosphorylation under mitotic arrest/stress, Co-IP, mutant rescue

    PMID:18328708

    Open questions at the time
    • Whether MST1 also directly phosphorylates LATS1 activation loop was not resolved
    • Relative contributions of MST1 vs MST2 to MOB1 phosphorylation in different tissues were untested
  6. 2009 High

    Demonstrating MST1 as a bona fide tumor suppressor in vivo: combined Mst1/Mst2 liver knockout abolished YAP Ser127 phosphorylation and caused hepatocellular carcinoma; re-expression of MST1 restored YAP phosphorylation and suppressed tumorigenicity.

    Evidence Conditional double-knockout mice, HCC cell line re-expression, phospho-specific immunoblotting

    PMID:19878874

    Open questions at the time
    • The intermediary kinase between MST1/2 and YAP Ser127 (distinct from LATS1/2) was unidentified
    • Whether MST1 alone is sufficient or MST2 redundancy is obligate was tissue-dependent and unresolved
  7. 2009 High

    Connecting MST1 to FOXO-dependent neuronal death and to mitotic control via NDR kinases and Aurora B: MST1 phosphorylates FOXO1 Ser212 to drive nuclear translocation and death, phosphorylates NDR1 for centrosome duplication, and inhibits Aurora B to stabilize kinetochore–microtubule attachments.

    Evidence In vitro kinase assays, primary neuron imaging, RNAi epistasis, shRNA-resistant rescue, chromosome alignment assay

    PMID:19221179 PMID:19836237 PMID:20171103

    Open questions at the time
    • How MST1 toggles between apoptotic (FOXO) and mitotic (NDR/Aurora B) substrates was unknown
    • Whether MST1 phosphorylation of Aurora B is direct or requires MOB1/NDR scaffolding was not fully resolved
  8. 2009 High

    Defining the Akt inhibitory phosphorylation: Akt phosphorylates MST1 at Thr120, blocking autophosphorylation, nuclear translocation, and downstream FOXO3a/JNK activation — establishing a direct survival-kinase brake on MST1.

    Evidence In vitro kinase assay, T120 mutagenesis, subcellular fractionation, downstream phosphorylation assays

    PMID:19940129

    Open questions at the time
    • Whether Thr120 phosphorylation affects SARAH-domain dimerization was not tested
  9. 2010 High

    Identifying PHLPP phosphatases as MST1 activators: PHLPP1/2 dephosphorylate the inhibitory Thr387 site to activate MST1, placing MST1 at a phosphorylation–dephosphorylation switch between Akt and PHLPP.

    Evidence Co-IP, direct phosphatase activity assay, downstream p38/JNK activation assays

    PMID:20513427

    Open questions at the time
    • Relative contribution of Thr120 vs Thr387 dephosphorylation to full MST1 reactivation was unresolved
  10. 2011 High

    Discovering the oxidative-stress activation mechanism: oxidized PRX-I oligomers directly bind MST1 and promote its autophosphorylation, establishing a redox-sensing input to Hippo signaling.

    Evidence In vitro reconstitution with purified PRX-I and MST1, RNAi knockdown, ROS measurement

    PMID:21516123

    Open questions at the time
    • Whether PRX-I acts catalytically or stoichiometrically on MST1 was unclear
    • Applicability beyond H2O2/cisplatin stimuli was untested
  11. 2012 High

    Extending MST1 function beyond growth control into adaptive immunity: MST1/2 control MOB1 phosphorylation downstream of S1P/CCL21, enabling Dock8-Rac1 activation and T-cell migration/thymic egress.

    Evidence Double-KO mice, GTP-loading assays, MOB1 phosphorylation, Co-IP (MOB1–Dock8), thymocyte migration assays

    PMID:22412158

    Open questions at the time
    • Whether MST1 directly phosphorylates Dock8 or acts only through MOB1 was unknown
  12. 2014 High

    Identifying multiple new MST1 substrates with tissue-specific consequences: MST1 phosphorylates Bcl-xL Ser14 to release Bax for apoptosis, PDX1 Thr11 to target beta-cell transcription factor degradation, and AURKA to promote ciliogenesis by disrupting the AURKA/HDAC6 disassembly complex.

    Evidence In vitro kinase assays with mutagenesis, Bax activation assay, ubiquitination/degradation assays, Mst1-KO mice, zebrafish cilia phenotype

    PMID:24633305 PMID:24813943 PMID:25367221

    Open questions at the time
    • Whether Bcl-xL phosphorylation is sufficient for apoptosis without concurrent FOXO/BIM induction was unclear
    • How MST1 localizes to the basal body for ciliogenesis was not determined
  13. 2015 High

    Revealing mTORC2 as an upstream inhibitor: mTORC2 phosphorylates MST1 at Ser438 in the SARAH domain, disrupting homodimerization and reducing kinase activity — cardiac-specific Rictor deletion hyperactivates MST1 and causes cardiomyopathy.

    Evidence In vitro kinase assay, dimerization assay, cardiac-specific Rictor-KO mice

    PMID:25843706

    Open questions at the time
    • Whether Ser438 phosphorylation promotes heterodimerization with MST2 was not tested
  14. 2016 High

    Uncovering how oncogenic Ras suppresses Hippo signaling: H-Ras/Erk promotes MST1/MST2 heterodimerization via SARAH domains, markedly reducing kinase activity; paradoxically, cells lacking MST1 resist Ras transformation because heterodimer-mediated suppression is abolished.

    Evidence Co-IP of SARAH domain interactions, in vitro kinase assay comparing homo- vs heterodimers, Mst1-KO cell transformation assay

    PMID:27238285

    Open questions at the time
    • Whether Erk directly phosphorylates MST1 or MST2 to promote heterodimerization was unknown
    • Structural basis for lower heterodimer activity was not resolved
  15. 2016 High

    Establishing a pharmacological tool: XMU-MP-1 was identified as a selective MST1/2 inhibitor with a co-crystal structure, enabling tissue repair via YAP activation in vivo.

    Evidence HTS enzyme assay, co-crystal structure, SAR, mouse intestinal/liver injury models

    PMID:27535619

    Open questions at the time
    • Off-target kinase spectrum beyond the tested panel was incomplete
    • Long-term oncogenic risk of sustained MST1/2 inhibition was not assessed
  16. 2017 Medium

    RASSF1A/RASSF5 binding redirects MST1 substrate specificity toward histone H2B (chromatin condensation) and away from FOXO, revealing scaffold-dependent substrate selectivity.

    Evidence SPR domain mapping of RASSF–MST1 interaction, in vitro kinase assays for H2B vs FOXO phosphorylation

    PMID:28327630

    Open questions at the time
    • Single lab; substrate switching not confirmed in cells or in vivo
    • Whether RASSF alters MST1 conformation or simply co-localizes it near H2B was unknown
  17. 2019 High

    Connecting MST1 to vascular biology: mitochondrial ROS activates MST1 in endothelial tip cells, driving FOXO1 nuclear import for tip-cell polarity and sprouting angiogenesis; separately, FGFR4 phosphorylates MST1 at Tyr433 to suppress its activity in HER2+ breast cancer.

    Evidence Endothelial-specific KO mice, retinal angiogenesis assay, MS-identified Y433 phosphorylation with mutagenesis, FGFR4 inhibitor studies

    PMID:30783090 PMID:30903103

    Open questions at the time
    • Whether FGFR4-mediated Tyr433 phosphorylation occurs in non-cancer endothelial contexts was untested
  18. 2020 High

    Identifying UNC5B as an MST1 substrate in dependence-receptor apoptosis: MST1 phosphorylates UNC5B Thr428 upon netrin withdrawal, promoting dopaminergic neuronal death relevant to Parkinson's disease pathology.

    Evidence In vitro kinase assay, Co-IP, T428 mutagenesis, UNC5B-KO mice, PD patient brain tissue

    PMID:32929029

    Open questions at the time
    • Whether MST1 inhibitors are neuroprotective in chronic PD models was not tested
  19. 2022 High

    Defining a hemichannel-regulatory function: MST1 phosphorylates Cx43 at Ser255, keeping hemichannels closed; disturbed flow inhibits MST1 and opens hemichannels to promote endothelial activation and atherosclerosis.

    Evidence MS substrate identification, proximity ligation, dye uptake hemichannel assay, EC-specific KO on ApoE-null background, phospho-mimetic rescue

    PMID:36164986

    Open questions at the time
    • Whether other Cx43 kinases compensate when MST1 is active was not tested
    • Mechanism by which disturbed flow inhibits MST1 was not elucidated
  20. 2024 Medium

    Revealing transcriptional and post-translational suppression by SIRT7: SIRT7 deacetylates H3K18 at the MST1 promoter to repress transcription and deacetylates MST1 protein to prime ubiquitination-dependent degradation, promoting YAP nuclear localization in HCC.

    Evidence ChIP, luciferase reporter, MS-identified deacetylation sites, Co-IP, ubiquitination assay

    PMID:38288904

    Open questions at the time
    • Single lab; the E3 ubiquitin ligase acting downstream of SIRT7-mediated deacetylation was not identified
    • Whether other sirtuins compensate for SIRT7 loss was untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for RASSF-mediated substrate switching, identification of the intermediary kinase between MST1/2 and YAP Ser127 distinct from LATS1/2, the mechanism by which mechanical forces (shear stress) regulate MST1 activity, and whether MST1's diverse substrate repertoire is controlled by tissue-specific scaffolds or by subcellular localization.
  • No structural model of MST1 in complex with RASSF or MOB1 scaffolds
  • Mechanism of mechanotransduction to MST1 is undefined
  • Tissue-specific substrate selection rules are unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 13 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-5357801 Programmed Cell Death 7 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
AKT1FOXO1LATS1MOB1ANDR1PHLPP1RASSF1ASAV1
Complex memberships
MST1/MOB1MST1/RASSF1AMST1/SAV1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 MST1 is activated by autophosphorylation at Thr183 (primary site) and Thr187 in subdomain VIII via intermolecular autophosphorylation enhanced by homodimerization; active MST1 also autophosphorylates at Thr177 and Thr387. Kinase activity (not caspase cleavage) is required for JNK and caspase activation and apoptotic morphological changes. In vitro kinase assay, site-directed mutagenesis, cell-based phosphorylation mapping The Journal of biological chemistry High 12223493
2001 MST1 contains two functional nuclear export signals (NES) in its C-terminal domain; caspase-mediated cleavage releases the C-terminal domain, allowing the N-terminal kinase fragment to translocate to the nucleus where it promotes chromatin condensation. NES mutation or leptomycin B treatment redirects full-length MST1 to the nucleus. NES mutagenesis, leptomycin B treatment, subcellular fractionation/immunofluorescence, staurosporine-induced apoptosis assay Proceedings of the National Academy of Sciences of the United States of America High 11517310
2008 MST1 and MST2 phosphorylate MOBKL1A and MOBKL1B (homologs of Drosophila MATS) as preferred substrates in vitro and in mitotic cells. MST1/2-catalyzed MOB phosphorylation promotes MOB binding to LATS1 and enables LATS1 activation loop phosphorylation; replacement with non-phosphorylatable MOB accelerates cell proliferation by speeding G1/S and mitotic exit. In vitro kinase assay, cell-based phosphorylation (okadaic acid/H2O2/mitotic arrest), Co-IP, non-phosphorylatable mutant rescue Current biology : CB High 18328708
2009 Combined Mst1/Mst2 deficiency in mouse liver causes loss of inhibitory Ser127 phosphorylation of YAP1 (Yorkie ortholog), massive hepatic overgrowth, and hepatocellular carcinoma. Re-expression of Mst1 in HCC cell lines restores YAP1 Ser127 phosphorylation and abrogates tumorigenicity. Mst1/2 inactivates YAP1 through an intermediary kinase distinct from Lats1/2. Conditional knockout mice, re-expression experiments in HCC cell lines, phospho-specific immunoblotting Cancer cell High 19878874
2009 MST1 phosphorylates FOXO1 at Ser212 (conserved with FOXO3 Ser207), disrupting FOXO1 association with 14-3-3 proteins and causing FOXO1 nuclear translocation. MST1 is required for neuronal cell death upon growth factor/activity deprivation, acting in a FOXO1-dependent manner. The scaffold protein Nore1 is required for this death signal. In vitro kinase assay, co-immunoprecipitation, primary neuron imaging (nuclear translocation), RNAi knockdown with apoptosis readout The Journal of biological chemistry High 19221179
2006 RASSF1A associates with MST1 in cells and co-localizes on microtubules throughout the cell cycle. Purified recombinant RASSF1A inhibits MST1 kinase activity in vitro, but overexpression of RASSF1A increases MST1 activity in intact cells. RASSF1A facilitates MST1 activation and Fas-induced apoptosis, as knockdown of RASSF1A reduces both. Co-immunoprecipitation, immunofluorescence colocalization, in vitro kinase assay with purified proteins, RNAi knockdown, Fas ligation apoptosis assay Cancer research High 16510573
2007 MST1 (STK4) is a physiological interaction partner of Akt1; both endogenous MST1 and MST2 inhibit endogenous Akt1 activity. Full-length MST1 and both caspase cleavage products (N- and C-terminal fragments) can complex with and inhibit Akt1. Co-IP from lipid raft-enriched fractions, kinase activity assay, zebrafish epistasis rescue experiment The EMBO journal Medium 17932490
2009 Akt phosphorylates MST1 at Thr120, inhibiting MST1 kinase activity, suppressing autophosphorylation at Thr183, and blocking nuclear translocation. Phospho-Thr120 MST1 fails to activate FOXO3a and JNK. In vitro kinase assay, site-directed mutagenesis, subcellular fractionation, downstream target phosphorylation assays The Journal of biological chemistry High 19940129
2010 PHLPP1 and PHLPP2 phosphatases bind MST1 (identified by co-IP in vitro and in vivo) and dephosphorylate MST1 at the inhibitory T387 site, thereby activating MST1 and its downstream effectors p38 and JNK to induce apoptosis. Akt phosphorylates the same T387 site to inhibit MST1. Co-immunoprecipitation in vivo and in vitro, phosphatase activity assay, downstream kinase assays Molecular cell High 20513427
2010 MST1 promotes accurate kinetochore-microtubule attachment by phosphorylating and inhibiting Aurora B kinase activity in vitro. MST1 and NDR1 associate with Aurora B; depletion of MST1 or NDR1 increases Aurora B activity, causes chromosome misalignment, and activates the spindle checkpoint. In vitro kinase assay (MST1 phosphorylates Aurora B), Co-IP, RNAi depletion, chromosome alignment assay Current biology : CB High 20171103
2009 MST1/hMOB1 signaling controls centrosome duplication via NDR kinase; MST1 phosphorylates NDR1 on its hydrophobic motif (required for centrosome duplication), and functional NDR1/hMOB1 complex formation is essential for this phosphorylation. RNAi depletion of MST1 or hMOB1 impairs centriole duplication. RNAi depletion, shRNA-resistant rescue constructs, phosphorylation assays, centrosome imaging Current biology : CB High 19836237
2011 Peroxiredoxin-I (PRX-I), when oxidized by H2O2 to form homo-oligomers, interacts with MST1 and promotes MST1 autophosphorylation and kinase activity. PRX-I is required for H2O2-induced MST1 activation; this was reconstituted in vitro with purified PRX-I and MST1. p53 mediates cisplatin-induced PRX-I oligomer formation and MST1 activation. In vitro reconstitution with purified proteins, RNAi knockdown, live-cell imaging (ROS), immunoprecipitation Oncogene High 21516123
2011 Daxx upregulated by IFN-γ mediates MST1 homodimerization, activation, and nuclear translocation in microglia, promoting activation-induced cell death. Depletion of Daxx or MST1 attenuates IFN-γ-induced microglial apoptosis. RNAi knockdown, subcellular fractionation, IFN-γ stimulation, Mst1-null mice The EMBO journal Medium 21572393
2012 Mst1 and Mst2 control sphingosine-1-phosphate- and CCL21-induced Mob1 phosphorylation, Rac1 and RhoA GTP loading, and subsequent T cell migration and thymic egress. Phospho-Mob1 binds and activates the Rac1 GEF Dock8 in thymocytes. Double KO mice, GTP-loading assays, Mob1 phosphorylation assay, Co-IP (Mob1-Dock8), thymocyte migration assays The Journal of experimental medicine High 22412158
2014 MST1 phosphorylates Bcl-xL at Ser14 within the BH4 domain, antagonizing Bcl-xL-Bax binding, thereby activating Bax and triggering mitochondria-mediated apoptosis. A K-Ras/RASSF1A/Mst1 signaling cassette localized to mitochondria mediates Mst1 activation by oxidative stress. In vitro kinase assay, site-directed mutagenesis, Co-IP, subcellular fractionation (mitochondrial localization), Bax activation assay Molecular cell High 24813943
2014 MST1 directly phosphorylates the beta cell transcription factor PDX1 at Thr11, leading to PDX1 ubiquitination and proteasomal degradation, causing impaired insulin secretion. MST1 also induces the BH3-only protein BIM to activate mitochondria-dependent apoptosis in beta cells. In vitro kinase assay, mass spectrometry, mutagenesis, ubiquitination assay, Mst1 KO mice Nature medicine High 24633305
2015 mTORC2 (Rictor complex) phosphorylates MST1 at Ser438 in the SARAH domain, reducing MST1 homodimerization and kinase activity. Cardiac-specific Rictor deletion leads to marked MST1 activation, cardiac dysfunction, and dilation. In vitro kinase assay, phosphorylation site mapping, dimerization assay, cardiac-specific KO mice Cell reports High 25843706
2014 The MST1/2-SAV1 complex promotes ciliogenesis: MST1 is activated during ciliogenesis, localizes to the basal body, phosphorylates Aurora kinase A (AURKA) causing dissociation of the AURKA/HDAC6 cilia-disassembly complex, and associates with the NPHP transition-zone complex to promote ciliary cargo localization. Immunofluorescence (basal body localization), in vitro kinase assay (MST1 phosphorylates AURKA), Co-IP (MST1-NPHP complex), zebrafish phenotype, siRNA depletion Nature communications High 25367221
2016 XMU-MP-1 is a selective, reversible MST1/2 inhibitor identified by ELISA-based HTS; co-crystal structure confirmed on-target binding. XMU-MP-1 blocks MST1/2 kinase activities, activates YAP, and promotes intestinal and liver repair in mouse injury models. HTS enzyme assay, co-crystal structure (MST1/2 with inhibitor), structure-activity relationship, mouse in vivo repair models Science translational medicine High 27535619
2016 H-ras promotes formation of Mst1/Mst2 heterodimers via their SARAH domains through an Erk-dependent mechanism; Mst1/Mst2 heterodimers have markedly reduced kinase activity compared to homodimers. Cells lacking Mst1, where heterodimers are impossible, are resistant to H-ras transformation and maintain active Hippo signaling. Co-IP (SARAH domain interaction), in vitro kinase assay comparing homo- vs. heterodimers, Mst1-KO cell transformation assay Current biology : CB High 27238285
2017 MST1 phosphorylates eIF4E, causing weaker 5' CAP binding and reduced mRNA translation, while simultaneously increasing lncRNA association with active polyribosomes. MST1-mediated eIF4E phosphorylation triggers production of a micropeptide STORM from linc00689. In vitro kinase assay, CAP-binding assay, polyribosome profiling, mass spectrometry Biochimica et biophysica acta. Gene regulatory mechanisms Medium 28487214
2017 RASSF1A and RASSF5 interact with MST1 through both the SARAH domain and the N-terminal kinase domain (mapped by SPR). RASSF-MST1 complex promotes MST1-H2B Ser14 phosphorylation (chromatin condensation marker) while suppressing MST1-FoxO phosphorylation, switching MST1's downstream substrate specificity. Surface plasmon resonance (SPR) domain mapping, in vitro kinase assays for H2B and FoxO phosphorylation Scientific reports Medium 28327630
2019 MST1 is activated by mitochondrial ROS produced in response to hypoxia in endothelial tip cells; activated MST1 promotes nuclear import of FOXO1, augmenting transcription of polarity and migration genes. Endothelial-specific deletion of MST1 or FOXO1 abolishes tip cell polarity and impairs sprouting angiogenesis. Endothelial-specific KO mice (MST1, FOXO1), ROS measurement, FOXO1 nuclear import imaging, retinal angiogenesis assay Nature communications High 30783090
2019 FGFR4 phosphorylates MST1 at Tyr433 (identified by mass spectrometry in COS-1 cells), suppressing MST1 kinase activity; Y433F mutation increases MST1 activation and downstream MOB1 phosphorylation. FGFR4 inhibition leads to increased MST1/2 activation, nuclear MST1 localization, and apoptosis in HER2+ breast cancer cells. Kinase substrate screen, mass spectrometry (Y433 site), Y433F mutagenesis, downstream phosphorylation assays, FGFR4 pharmacological inhibition Cell death and differentiation High 30903103
2020 Netrin1 deprivation activates MST1, which selectively binds and phosphorylates the netrin receptor UNC5B at Thr428, promoting UNC5B apoptotic activation and dopaminergic neuronal loss. UNC5B knockout abolishes netrin depletion-induced dopaminergic loss; blocking MST1 phosphorylation of UNC5B suppresses neuronal apoptosis. In vitro kinase assay, Co-IP (MST1-UNC5B), site-directed mutagenesis (T428), UNC5B-KO mice, PD patient brain tissue validation Proceedings of the National Academy of Sciences of the United States of America High 32929029
2014 USP46 (deubiquitinase) directly binds MST1 and decreases its ubiquitination, stabilizing MST1 protein and potentiating its kinase activity to promote YAP1 degradation in hepatocellular carcinoma. Co-immunoprecipitation, ubiquitination assay, gain/loss-of-function, xenograft model Experimental cell research Medium 34029571
2014 MST1 overexpression in cardiomyocytes promotes Beclin1 binding to Bcl-2 (sequestering Bcl-2) and causes Bcl-2 to dissociate from Bax, leading to autophagy suppression and apoptosis induction; conversely Mst1 knockout disrupts the Beclin1-Bcl-2 complex and enhances autophagy. Co-immunoprecipitation, Mst1 transgenic and KO mice with streptozotocin-induced diabetes, autophagic flux assay Diabetologia Medium 27510910
2014 MST1 translocates to mitochondria upon gemcitabine treatment (ROS-dependent) and forms a complex with cyclophilin D (Cyp-D); this MST1/Cyp-D mitochondrial complex is required for gemcitabine-induced pancreatic cancer cell death. Subcellular fractionation, Co-IP (MST1-CypD), ROS inhibition (NAC), CypD inhibitor (CsA), shRNA knockdown Biochimie Medium 24732633
2022 MST1 phosphorylates connexin 43 (Cx43) at Ser255 in endothelial cells; oscillatory shear stress (disturbed flow) inhibits MST1 activity, reducing Cx43 Ser255 phosphorylation, opening Cx43 hemichannels, and activating endothelial cells to promote atherosclerosis. Filamin B fuels Cx43 translocation to lipid rafts for hemichannel opening. Mass spectrometry substrate identification, Co-IP, proximity ligation assay, dye uptake assay (hemichannel opening), EC-specific KO on ApoE background, lentiviral phospho-mimetic rescue Circulation research High 36164986
2023 MST1 phosphorylates the nuclear receptor Nur77 at Thr366, identified by in vitro kinase assay and LC-MS/MS, promoting Nur77 transcriptional activity and upregulating β3-integrin expression to enhance endometrial receptivity. Phospho-Nur77 (T366) levels are reduced in women with recurrent implantation failure. In vitro kinase assay, LC-MS/MS phosphosite identification, phos-tag SDS-PAGE, phospho-specific antibody, embryo adhesion assay, delayed implantation mouse model EBioMedicine High 36623453
2024 SIRT7 suppresses MST1 by (1) binding to the MST1 promoter and inducing H3K18 deacetylation to repress transcription, and (2) directly binding and deacetylating MST1 protein, priming acetylation-dependent MST1 ubiquitination and degradation, thereby promoting YAP nuclear localization in HCC. ChIP, luciferase reporter assay, mass spectrometry (deacetylation sites), Co-IP, ubiquitination assay, YAP localization imaging Cancer science Medium 38288904
2016 MST1 regulates CD19 mRNA levels in B cells via the transcription factor TEAD2, which binds a consensus motif in the CD19 3' UTR; Mst1-deficient mice show reduced BCR signaling, defective BCR clustering, and impaired B-cell spreading, with consequent MZ and GC B-cell differentiation defects. Mst1-KO mice, TIRF microscopy (BCR clustering), ChIP (TEAD2 on cd19 3'UTR), qRT-PCR, lipid bilayer assay Blood advances Medium 29296937
2016 MST1 deficiency in dendritic cells promotes IL-6 secretion via p38 MAPK pathway activation, which in turn increases STAT3 activation in CD4+ T cells to drive Th17 differentiation; ectopic MST1 expression in DCs inhibits Th17 differentiation. DC-specific KO, cytokine ELISA, p38/STAT3 phosphorylation assays, gain-of-function (ectopic MST1), EAE and antifungal models Nature communications Medium 28145433

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer cell 791 19878874
2010 Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proceedings of the National Academy of Sciences of the United States of America 473 20080598
2008 MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Current biology : CB 357 18328708
2016 Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Science translational medicine 330 27535619
1994 RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. The EMBO journal 280 8062829
2014 MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes. Nature medicine 182 24633305
1991 Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. Biochemistry 171 1655021
2003 The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration. Developmental cell 168 12919677
2002 Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation. The Journal of biological chemistry 164 12223493
2013 MSP-RON signalling in cancer: pathogenesis and therapeutic potential. Nature reviews. Cancer 162 23792360
2006 Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. Cancer research 161 16510573
2009 Regulation of neuronal cell death by MST1-FOXO1 signaling. The Journal of biological chemistry 160 19221179
2017 Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling. Journal of pineal research 151 28480597
2001 Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation. Proceedings of the National Academy of Sciences of the United States of America 147 11517310
2012 The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. The Journal of experimental medicine 142 22412158
2009 Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes. The EMBO journal 140 19339990
2008 The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proceedings of the National Academy of Sciences of the United States of America 134 19073936
2014 Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL. Molecular cell 124 24813943
2007 The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1. The EMBO journal 118 17932490
2015 mTORC2 regulates cardiac response to stress by inhibiting MST1. Cell reports 116 25843706
2009 Crucial role for Mst1 and Mst2 kinases in early embryonic development of the mouse. Molecular and cellular biology 115 19786569
2016 MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in mice. Diabetologia 107 27510910
2010 Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis. Molecular cell 107 20513427
2018 Mst1 promotes cardiac ischemia-reperfusion injury by inhibiting the ERK-CREB pathway and repressing FUNDC1-mediated mitophagy. The journal of physiological sciences : JPS 104 29961191
2010 Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development. British journal of cancer 92 21102585
2009 The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation. Current biology : CB 92 19836237
1995 Expression of HGF/SF, HGF1/MSP, and c-met suggests new functions during early chick development. Developmental genetics 83 7554499
2018 Mst1 inhibits Sirt3 expression and contributes to diabetic cardiomyopathy through inhibiting Parkin-dependent mitophagy. Biochimica et biophysica acta. Molecular basis of disease 81 29674007
2013 Mst1 and Mst2 kinases: regulations and diseases. Cell & bioscience 80 23985272
2016 MST1/MST2 Protein Kinases: Regulation and Physiologic Roles. Biochemistry 76 27618557
2019 A MST1-FOXO1 cascade establishes endothelial tip cell polarity and facilitates sprouting angiogenesis. Nature communications 74 30783090
2011 Oligomeric peroxiredoxin-I is an essential intermediate for p53 to activate MST1 kinase and apoptosis. Oncogene 74 21516123
2004 Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Oncogene 74 15007383
2017 Dendritic cell MST1 inhibits Th17 differentiation. Nature communications 71 28145433
2014 The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis. Nature communications 71 25367221
2016 Melatonin alleviates postinfarction cardiac remodeling and dysfunction by inhibiting Mst1. Journal of pineal research 70 27696525
2008 Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Mucosal immunology 69 19079170
2009 Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120. The Journal of biological chemistry 68 19940129
1989 The DNF15S2 locus at 3p21 is transcribed in normal lung and small cell lung cancer. Genomics 64 2565880
2018 Mst1 regulates post-infarction cardiac injury through the JNK-Drp1-mitochondrial fission pathway. Cellular & molecular biology letters 55 29760744
2013 MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells. Biochemical and biophysical research communications 54 24134840
2015 A conserved MST1/2-YAP axis mediates Hippo signaling during lung growth. Developmental biology 53 25912685
2020 Tubule-Specific Mst1/2 Deficiency Induces CKD via YAP and Non-YAP Mechanisms. Journal of the American Society of Nephrology : JASN 50 32253273
2018 Melatonin Regulates Apoptosis and Autophagy Via ROS-MST1 Pathway in Subarachnoid Hemorrhage. Frontiers in molecular neuroscience 50 29632474
2006 Repression of the MSP/MST-1 gene contributes to the antiapoptotic gain of function of mutant p53. Oncogene 50 16170349
2019 FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2-dependent apoptosis. Cell death and differentiation 49 30903103
2014 Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway. Journal of neuro-oncology 48 25373346
2017 Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1. Biochemical and biophysical research communications 46 29127009
2013 Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. PloS one 46 24040101
2016 MST1: a promising therapeutic target to restore functional beta cell mass in diabetes. Diabetologia 45 27053234
2011 Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling. The EMBO journal 45 21572393
2017 eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation. Biochimica et biophysica acta. Gene regulatory mechanisms 44 28487214
2010 MST1 limits the kinase activity of aurora B to promote stable kinetochore-microtubule attachment. Current biology : CB 43 20171103
1999 Kinases involved in MSP/RON signaling. Journal of leukocyte biology 43 10080538
2014 Genetic deletion of Mst1 alters T cell function and protects against autoimmunity. PloS one 41 24852423
2020 Mst1 knockdown alleviates cardiac lipotoxicity and inhibits the development of diabetic cardiomyopathy in db/db mice. Biochimica et biophysica acta. Molecular basis of disease 40 32320827
2021 CCL2 regulation of MST1-mTOR-STAT1 signaling axis controls BCR signaling and B-cell differentiation. Cell death and differentiation 39 33879857
2020 Netrin1 deficiency activates MST1 via UNC5B receptor, promoting dopaminergic apoptosis in Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 39 32929029
2014 Gemcitabine-induced pancreatic cancer cell death is associated with MST1/cyclophilin D mitochondrial complexation. Biochimie 38 24732633
2022 MST1 Suppresses Disturbed Flow Induced Atherosclerosis. Circulation research 35 36164986
2014 Overexpression of MYC and EZH2 cooperates to epigenetically silence MST1 expression. Epigenetics 34 24499724
2018 Genetic diversity of the msp-1, msp-2, and glurp genes of Plasmodium falciparum isolates in Northwest Ethiopia. Malaria journal 33 30359280
2005 MSP domain proteins. Trends in parasitology 32 15837611
2000 Clonality analysis by methylation-specific PCR for the human androgen-receptor gene (HUMARA-MSP). Leukemia 32 10637497
2020 LncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through Mst1. Cell cycle (Georgetown, Tex.) 31 32627655
2020 MSP-RON Pathway: Potential Regulator of Inflammation and Innate Immunity. Frontiers in immunology 31 33117355
2014 Constitutively active NDR1-PIF kinase functions independent of MST1 and hMOB1 signalling. Cellular signalling 30 24747552
2017 Understanding the role of mammalian sterile 20-like kinase 1 (MST1) in cardiovascular disorders. Journal of molecular and cellular cardiology 29 29155025
2024 SIRT7 promotes Hippo/YAP activation and cancer cell proliferation in hepatocellular carcinoma via suppressing MST1. Cancer science 28 38288904
2024 Inhibition of MST1 ameliorates neuronal apoptosis via GSK3β/β-TrCP/NRF2 pathway in spinal cord injury accompanied by diabetes. Redox biology 28 38430683
2017 TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 28802229
2016 H-ras Inhibits the Hippo Pathway by Promoting Mst1/Mst2 Heterodimerization. Current biology : CB 26 27238285
2016 Mst1 positively regulates B-cell receptor signaling via CD19 transcriptional levels. Blood advances 26 29296937
2006 Sperm motility and MSP. WormBook : the online review of C. elegans biology 26 18050481
2001 Anti-apoptotic action of macrophage stimulating protein (MSP). Apoptosis : an international journal on programmed cell death 26 11388667
2020 Hippo kinases MST1 and MST2 control the differentiation of the epididymal initial segment via the MEK-ERK pathway. Cell death and differentiation 25 32332916
2016 Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis. Experimental cell research 25 27793648
2003 Phylogenetic analysis of CSP and MSP-9 gene sequences demonstrates the close relationship of Plasmodium coatneyi to Plasmodium knowlesi. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 25 12797974
2018 Mst1/2 Kinases Modulate Glucose Uptake for Osteoblast Differentiation and Bone Formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 24 29474739
2017 Rassf Proteins as Modulators of Mst1 Kinase Activity. Scientific reports 24 28327630
2021 Deubiquitinating enzyme USP46 suppresses the progression of hepatocellular carcinoma by stabilizing MST1. Experimental cell research 23 34029571
2014 RASSF5 inhibits growth and invasion and induces apoptosis in osteosarcoma cells through activation of MST1/LATS1 signaling. Oncology reports 23 25109282
2019 New Insights into Multistep-Phosphorelay (MSP)/ Two-Component System (TCS) Regulation: Are Plants and Bacteria that Different? Plants (Basel, Switzerland) 22 31835810
2017 HGFL-mediated RON signaling supports breast cancer stem cell phenotypes via activation of non-canonical β-catenin signaling. Oncotarget 22 28938607
2014 Genetic diversity of the msp-1, msp-2, and glurp genes of Plasmodium falciparum isolates along the Thai-Myanmar borders. Asian Pacific journal of tropical biomedicine 22 25183327
2010 MSP hormonal control of the oocyte MAP kinase cascade and reactive oxygen species signaling. Developmental biology 22 20380830
2023 Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice. EBioMedicine 21 36623453
2020 MST1/2 Balance Immune Activation and Tolerance by Orchestrating Adhesion, Transcription, and Organelle Dynamics in Lymphocytes. Frontiers in immunology 21 32435241
2012 Role of major sperm protein (MSP) in the protrusion and retraction of Ascaris sperm. International review of cell and molecular biology 21 22608562
2012 Tumor suppressor Hippo/MST1 kinase mediates chemotaxis by regulating spreading and adhesion. Proceedings of the National Academy of Sciences of the United States of America 21 22847424
2020 SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy. Aging 20 31951593
2020 Hippo Kinases MST1/2 Regulate Immune Cell Functions in Cancer, Infection, and Autoimmune Diseases. Critical reviews in eukaryotic gene expression 20 33389879
2014 Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. PloS one 20 25133611
2022 XMU-MP-1 protects heart from ischemia/reperfusion injury in mice through modulating Mst1/AMPK pathway. European journal of pharmacology 19 35123978
2018 The Role of Mst1 in Lymphocyte Homeostasis and Function. Frontiers in immunology 19 29459865
2008 Polymorphism in the Plasmodium vivax msp 3: gene in field samples from Tierralta, Colombia. Memorias do Instituto Oswaldo Cruz 19 18797765
1997 Evolution of plasminogen-related growth factors (HGF/SF and HGF1/MSP). Ciba Foundation symposium 19 9524762
2023 Multisystem proteinopathies (MSPs) and MSP-like disorders: Clinical-pathological-molecular spectrum. Annals of clinical and translational neurology 18 36861178
2014 Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. PloS one 18 24595170
2003 Expression and purification of Plasmodium falciparum MSP-1(42): A malaria vaccine candidate. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 18 12651002