Affinage

PSMC6

26S proteasome regulatory subunit 10B · UniProt P62333

Round 2 corrected
Length
389 aa
Mass
44.2 kDa
Annotated
2026-04-28
130 papers in source corpus 8 papers cited in narrative 8 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMC6 (Rpt4/S10b) is one of six AAA-ATPase subunits that form the heterohexameric ring of the 19S regulatory particle of the 26S proteasome, where it powers ATP-dependent unfolding and translocation of ubiquitinated substrates into the 20S catalytic core for degradation (PMID:8811196, PMID:19489727). Genome-wide CRISPR screening in multiple myeloma cells established that loss of PSMC6 confers resistance to the proteasome inhibitor bortezomib by reducing inhibition of chymotrypsin-like proteasome activity, a property shared by all six 19S ATPase subunits (PMID:28958990). In osteoblasts, PSMC6 promotes apoptosis through suppression of PI3K/AKT signaling, and its knockout in an ovariectomy-induced osteoporosis mouse model elevates bone mineral density (PMID:32017075).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1996 High

    Establishing that the 26S proteasome — including its six AAA-ATPase ring subunits such as PSMC6 — is the principal ATP-dependent protease for ubiquitin-conjugated substrates resolved the long-standing question of how cells selectively degrade marked proteins.

    Evidence Biochemical reconstitution, subunit purification, peptidase assays, and structural analysis of 19S and 20S particles

    PMID:8811196

    Open questions at the time
    • Individual contributions of each ATPase subunit to the unfolding cycle were not resolved
    • No structural model at atomic resolution for the mammalian 19S ring at this time
  2. 2009 High

    Detailed mechanistic analysis showed how the six-ATPase ring (including PSMC6) couples ATP hydrolysis to substrate unfolding and threading, and revealed that proteasome-associated deubiquitinases gate substrate commitment versus escape, clarifying the decision point before irreversible degradation.

    Evidence Biochemical reconstitution with mutant ATPase subunits and structural studies of proteasome ATPase ring; complemented by large-scale AP-MS mapping proteasome–DUB interactions

    PMID:19489727 PMID:19615732

    Open questions at the time
    • PSMC6-specific catalytic contribution within the ATPase ring not individually dissected
    • Structural basis for ordered ATP hydrolysis around the ring not yet available
  3. 2013 Medium

    PARKIN-dependent ubiquitylation of mitochondrial outer membrane substrates upon depolarization was shown to funnel substrates to the proteasome, linking the PSMC6-containing 19S particle to mitophagy-associated protein turnover and broadening the physiological contexts of proteasomal degradation.

    Evidence Quantitative diGly-capture proteomics and AP-MS detecting PARKIN–proteasome association

    PMID:23503661

    Open questions at the time
    • PSMC6 role inferred as part of intact proteasome; no subunit-specific perturbation performed
    • Whether PARKIN substrates are preferentially handled by a PSMC6-dependent sub-pathway is unknown
  4. 2015 Medium

    Systematic proteome-scale interaction mapping confirmed PSMC6's co-complex associations with other 19S regulatory particle subunits, providing an unbiased human interaction network for the proteasome.

    Evidence BioPlex high-throughput AP-MS in HEK293T cells

    PMID:26186194

    Open questions at the time
    • Interactions not individually validated for PSMC6 beyond co-complex membership
    • Dynamic or cell-type-specific interaction partners not explored
  5. 2017 High

    CRISPR screening revealed that PSMC6 loss is sufficient to confer bortezomib resistance in myeloma cells by reducing proteasome inhibition, answering the question of which genetic determinants govern clinical proteasome-inhibitor sensitivity.

    Evidence Two independent genome-wide CRISPR screens with secondary targeted validation and chymotrypsin-like activity assays in multiple myeloma cells

    PMID:28958990

    Open questions at the time
    • Mechanism by which 19S ATPase loss alters 20S active-site accessibility to bortezomib not biochemically resolved
    • Whether PSMC6 loss affects drug sensitivity in other cancer types remains untested
  6. 2020 Medium

    Discovery that PSMC6 promotes osteoblast apoptosis via PI3K/AKT pathway suppression — and that its knockout in vivo improves bone density in osteoporosis — established a non-canonical, cell-type-specific role for PSMC6 beyond bulk proteolysis.

    Evidence Ovariectomy-induced osteoporosis mouse model with PSMC6 knockout, siRNA knockdown, overexpression, and PI3K/AKT pathway analysis by Western blot and flow cytometry

    PMID:32017075

    Open questions at the time
    • Whether apoptosis promotion is a direct effect of PSMC6 or secondary to altered proteasomal degradation of PI3K/AKT pathway components is unresolved
    • Pathway placement relies on inhibitor and overexpression studies rather than direct biochemical reconstitution
  7. 2021 Low

    siRNA-mediated silencing of PSMC6 in lung adenocarcinoma cells reduced proliferation, migration, and invasion, with bioinformatic inference suggesting WNT pathway activation via proteasomal AXIN degradation as a potential mechanism.

    Evidence siRNA knockdown with proliferation/migration/invasion assays and gene set enrichment analysis in lung adenocarcinoma cell lines

    PMID:34239933

    Open questions at the time
    • No direct biochemical evidence that PSMC6 specifically promotes AXIN degradation
    • WNT pathway link is inferred computationally, not validated experimentally
    • Single study without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • The specific mechanistic contribution of PSMC6 versus the other five 19S ATPase subunits to the ordered ATP hydrolysis cycle, substrate engagement selectivity, and proteasome assembly remains unresolved.
  • No subunit-specific reconstitution distinguishing PSMC6 from other ATPases in the ring
  • Structural basis for PSMC6's unique role in bortezomib sensitivity not determined
  • Whether PSMC6-dependent apoptotic signaling in osteoblasts is proteasome-dependent or reflects a moonlighting function is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 1
Partners
PRKNPSMC1PSMC2PSMC3PSMC4PSMC5PSMD14
Complex memberships
19S regulatory particle26S proteasome

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 The 26S proteasome (of which PSMC6/Rpt4 is one of six AAA-ATPase subunits in the 19S regulatory particle) was established as the ATP-dependent protease responsible for degrading ubiquitinated proteins. The six ATPases form a ring that drives substrate unfolding and translocation into the 20S core particle. Biochemical reconstitution, subunit purification, peptidase activity assays, structural analysis of 20S and 19S particles Annual review of biochemistry High 8811196
2009 PSMC6, as part of the six-ATPase ring of the 19S regulatory particle, participates in ATP-dependent substrate unfolding and translocation into the 20S core for degradation. Deubiquitinating enzymes (DUBs) associated with the regulatory particle can remove ubiquitin either to allow substrate degradation or to permit substrate escape before degradation initiates. Biochemical reconstitution, mutant analysis, structural studies of proteasome ATPase ring function Annual review of biochemistry High 19489727
2009 Affinity-purification mass spectrometry of 75 human deubiquitinating enzymes identified PSMC6 (as a 19S proteasome ATPase subunit) as part of proteasome-associated protein complexes linked to protein turnover, providing a protein-interaction landscape for the proteasome regulatory particle. Affinity-purification mass spectrometry (CompPASS platform), reciprocal interaction proteomics Cell Medium 19615732
2013 PARKIN-dependent ubiquitylation of mitochondrial outer membrane proteins upon depolarization was found to direct substrates to the proteasome (including the PSMC6-containing 19S regulatory particle), with depolarization-dependent PARKIN association detected with the proteasome by interaction proteomics. Quantitative diGly capture proteomics, affinity-purification mass spectrometry Nature Medium 23503661
2015 BioPlex AP-MS network identified interaction partners of PSMC6 in HEK293T cells, placing it within the 19S proteasome regulatory particle complex and revealing its co-complex associations with other proteasome subunits at proteome scale. High-throughput affinity-purification mass spectrometry (BioPlex) Cell Medium 26186194
2017 Genome-wide CRISPR screening in multiple myeloma cells identified PSMC6 as the sole validated gene whose loss reproducibly confers resistance to bortezomib (a proteasome inhibitor). Loss of PSMC6 significantly reduced inhibition of chymotrypsin-like proteasome activity by bortezomib, demonstrating that PSMC6 is required for bortezomib's mechanism of action. Individual knockout of each PSMC1–PSMC5 subunit also conferred bortezomib resistance, indicating a shared requirement for 19S ATPase subunits in drug sensitivity. Genome-wide CRISPR sgRNA library screen, secondary targeted CRISPR screen with 4 sgRNAs/gene, individual gene validation, proteasome chymotrypsin-like activity assay Molecular cancer therapeutics High 28958990
2020 PSMC6 promotes osteoblast apoptosis by inhibiting the PI3K/AKT signaling pathway. In an ovariectomy-induced osteoporosis mouse model, PSMC6 knockout elevated bone mineral density and increased PI3K phosphorylation, while PSMC6 overexpression promoted apoptosis (increased cleaved caspase-3/-9) and inhibited cell cycle progression and proliferation. PI3K activation significantly decreased PSMC6-induced osteoblast apoptosis, acting via p53, cyclinD1, and cleaved caspase-3/9 protein levels. Knockout mouse model (OVX osteoporosis), siRNA knockdown, overexpression, MTT assay, BrdU assay, flow cytometry, Western blot for PI3K/AKT pathway components and apoptosis markers Journal of cellular physiology Medium 32017075
2021 Silencing of PSMC6 by siRNA in lung adenocarcinoma cell lines inhibited cell growth, migration, and invasion. Bioinformatic analysis suggested PSMC6 overexpression may activate WNT signaling by promoting proteasomal degradation of AXIN protein, and PSMC6 expression was positively correlated with other proteasome subunits (PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, PSMD14). siRNA knockdown, cell proliferation/migration/invasion assays, gene set enrichment analysis, correlation analysis of proteasome subunit co-expression BioMed research international Low 34239933

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Structure and functions of the 20S and 26S proteasomes. Annual review of biochemistry 2108 8811196
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 1924 12167863
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annual review of biochemistry 1398 19489727
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2003 Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 1236 12808466
2003 DNA deamination mediates innate immunity to retroviral infection. Cell 1150 12809610
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science (New York, N.Y.) 1006 14564014
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2003 The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 912 12808465
2013 Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 870 23503661
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nature medicine 798 14528300
2003 Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 763 12859895
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2003 HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nature medicine 679 14528301
1999 p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1. The Journal of biological chemistry 677 10551817
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2003 HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Molecular cell 607 14527406
2003 Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science (New York, N.Y.) 570 12750511
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
1996 Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation. The Journal of biological chemistry 492 8798683
2013 Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nature genetics 463 23535732
2005 Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell 443 16239144
1999 Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation. Science (New York, N.Y.) 360 10617468
1998 p42/p44 MAP kinase module plays a key role in the transcriptional regulation of the vascular endothelial growth factor gene in fibroblasts. The Journal of biological chemistry 280 9660776
2002 Identification of two Sp1 phosphorylation sites for p42/p44 mitogen-activated protein kinases: their implication in vascular endothelial growth factor gene transcription. The Journal of biological chemistry 267 11904305
2004 Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway. Circulation research 230 15256482
1998 Growth factor-induced p42/p44 MAPK nuclear translocation and retention requires both MAPK activation and neosynthesis of nuclear anchoring proteins. The Journal of cell biology 188 9700154
2000 Signaling angiogenesis via p42/p44 MAP kinase and hypoxia. Biochemical pharmacology 168 11007955
1997 The p42/p44 mitogen-activated protein kinase cascade is determinant in mediating activation of the Na+/H+ exchanger (NHE1 isoform) in response to growth factors. The Journal of biological chemistry 159 8995258
2003 A novel role for FAK as a protease-targeting adaptor protein: regulation by p42 ERK and Src. Current biology : CB 158 12932330
2006 Role of caveolin-1 in p42/p44 MAP kinase activation and proliferation of human airway smooth muscle. American journal of physiology. Lung cellular and molecular physiology 152 16617096
2003 Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor kappaB in PBMCs. Diabetes 151 12606501
1988 Protein kinase C mediates platelet-derived growth factor-induced tyrosine phosphorylation of p42. The Journal of cell biology 150 2452172
1999 EPAS1 trans-activation during hypoxia requires p42/p44 MAPK. The Journal of biological chemistry 145 10559262
2002 PI3 kinase and not p42/p44 appears to be implicated in the protection conferred by ischemic preconditioning. Journal of molecular and cellular cardiology 142 12054853
1995 Distinct regions of the granulocyte colony-stimulating factor receptor are required for tyrosine phosphorylation of the signaling molecules JAK2, Stat3, and p42, p44MAPK. Blood 142 7579336
1999 PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits. The American journal of physiology 139 10330229
1999 Interleukin-1beta regulation of inducible nitric oxide synthase and cyclooxygenase-2 involves the p42/44 and p38 MAPK signaling pathways in cardiac myocytes. Hypertension (Dallas, Tex. : 1979) 138 9931117
2002 Early activation of the p42/p44MAPK pathway mediates adenosine-induced nitric oxide production in human endothelial cells: a novel calcium-insensitive mechanism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 136 12374781
1994 Real-time DNA binding measurements of the ETS1 recombinant oncoproteins reveal significant kinetic differences between the p42 and p51 isoforms. Protein science : a publication of the Protein Society 135 8003962
1991 p42/mitogen-activated protein kinase as a converging target for different growth factor signaling pathways: use of pertussis toxin as a discrimination factor. Cell regulation 130 1777507
1999 P42/44 MAP kinase inhibitor PD98059 attenuates multiple forms of synaptic plasticity in rat dentate gyrus in vitro. Journal of neurophysiology 122 9914271
2000 Signaling angiogenesis via p42/p44 MAP kinase cascade. Annals of the New York Academy of Sciences 117 10865838
1999 Lipopolysaccharide induces cholangiocyte proliferation via an interleukin-6-mediated activation of p44/p42 mitogen-activated protein kinase. Hepatology (Baltimore, Md.) 99 10094943
2001 The transcriptional co-activators CBP and p300 are activated via phenylephrine through the p42/p44 MAPK cascade. The Journal of biological chemistry 85 11705990
2002 Inhibition of LPS-induced p42/44 MAP kinase activation and iNOS/NO synthesis by parthenolide in rat primary microglial cells. Journal of neuroimmunology 82 12417429
2012 p42/p44-MAPK and PI3K are sufficient for IL-6 family cytokines/gp130 to signal to hypertrophy and survival in cardiomyocytes in the absence of JAK/STAT activation. Cellular signalling 81 23268184
2000 Simultaneous activation of p38 MAPK and p42/44 MAPK by ATP stimulates the K+ current ITREK in cardiomyocytes. The Journal of biological chemistry 81 10993907
2000 Lysophosphatidylcholine activates p38 and p42/44 mitogen-activated protein kinases in monocytic THP-1 cells, but only p38 activation is involved in its stimulated chemotaxis. Circulation research 77 10884372
2007 Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA(1), p42 and p38alpha. Biochimica et biophysica acta 75 17531530
2000 Sustained activation of p42/p44 mitogen-activated protein kinase during recovery from simulated ischaemia mediates adaptive cytoprotection in cardiomyocytes. The Biochemical journal 72 10970806
1996 Inhibition of tumor necrosis factor-induced p42/p44 mitogen-activated protein kinase activation by sodium salicylate. The Journal of biological chemistry 72 8626494
2004 PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation. American journal of physiology. Heart and circulatory physiology 70 15626689
1992 Activation of protein serine/threonine kinases p42, p63, and p87 in Rous sarcoma virus-transformed cells: signal transduction/transformation-dependent MBP kinases. Molecular biology of the cell 70 1337288
2013 Increase of mesenchymal stem cell migration by cannabidiol via activation of p42/44 MAPK. Biochemical pharmacology 69 24304686
2006 Sphingosine-1-phosphate induces COX-2 expression via PI3K/Akt and p42/p44 MAPK pathways in rat vascular smooth muscle cells. Journal of cellular physiology 66 16508949
2005 Involvement of p42/p44 MAPK, JNK, and NF-kappaB in IL-1beta-induced ICAM-1 expression in human pulmonary epithelial cells. Journal of cellular physiology 65 15389584
2009 The Arabidopsis proteasome RPT5 subunits are essential for gametophyte development and show accession-dependent redundancy. The Plant cell 60 19223514
2006 BK-induced COX-2 expression via PKC-delta-dependent activation of p42/p44 MAPK and NF-kappaB in astrocytes. Cellular signalling 59 16935468
1997 PMA-induced activation of the p42/44ERK- and p38RK-MAP kinase cascades in HL-60 cells is PKC dependent but not essential for differentiation to the macrophage-like phenotype. Journal of cellular physiology 57 9369943
2000 Fish oil modulates macrophage P44/P42 mitogen-activated protein kinase activity induced by lipopolysaccharide. JPEN. Journal of parenteral and enteral nutrition 56 10850941
2010 EV71 induces COX-2 expression via c-Src/PDGFR/PI3K/Akt/p42/p44 MAPK/AP-1 and NF-kappaB in rat brain astrocytes. Journal of cellular physiology 55 20333648
2003 p42, a novel cyclin-dependent kinase-activating kinase in mammalian cells. The Journal of biological chemistry 55 14597612
2000 P42 movement protein of Beet necrotic yellow vein virus is targeted by the movement proteins P13 and P15 to punctate bodies associated with plasmodesmata. Molecular plant-microbe interactions : MPMI 55 10796018
2001 The p42/p44 mitogen-activated protein kinase activation triggers p27Kip1 degradation independently of CDK2/cyclin E in NIH 3T3 cells. The Journal of biological chemistry 54 11418594
1997 Induction of a G2-phase arrest in Xenopus egg extracts by activation of p42 mitogen-activated protein kinase. Molecular biology of the cell 54 9362060
2004 Rosiglitazone ameliorates insulin resistance in brown adipocytes of Wistar rats by impairing TNF-alpha induction of p38 and p42/p44 mitogen-activated protein kinases. Diabetologia 53 15365619
2008 Tumor necrosis factor-alpha induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclear factor-kappaB in A549 cells. Toxicology and applied pharmacology 52 18336852
2001 Ionomycin causes activation of p38 and p42/44 mitogen-activated protein kinases in human neutrophils. American journal of physiology. Cell physiology 52 11401859
2000 Activation of Wee1 by p42 MAPK in vitro and in cycling xenopus egg extracts. Molecular biology of the cell 51 10712507
1998 Inhibition of p42 and p44 MAP kinase does not alter smooth muscle contraction in swine carotid artery. The American journal of physiology 51 9688905
2008 CTGF is increased in basal deposits and regulates matrix production through the ERK (p42/p44mapk) MAPK and the p38 MAPK signaling pathways. Investigative ophthalmology & visual science 50 19011018
2020 PSMC6 promotes osteoblast apoptosis through inhibiting PI3K/AKT signaling pathway activation in ovariectomy-induced osteoporosis mouse model. Journal of cellular physiology 49 32017075
2017 Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chemico-biological interactions 49 28601556
2017 CRISPR Genome-Wide Screening Identifies Dependence on the Proteasome Subunit PSMC6 for Bortezomib Sensitivity in Multiple Myeloma. Molecular cancer therapeutics 49 28958990
2005 Extracellular cysteine/cystine redox regulates the p44/p42 MAPK pathway by metalloproteinase-dependent epidermal growth factor receptor signaling. American journal of physiology. Gastrointestinal and liver physiology 48 15746213
2006 BK-induced cytosolic phospholipase A2 expression via sequential PKC-delta, p42/p44 MAPK, and NF-kappaB activation in rat brain astrocytes. Journal of cellular physiology 47 15991247
2002 Association between alphavbeta6 integrin expression, elevated p42/44 kDa MAPK, and plasminogen-dependent matrix degradation in ovarian cancer. Journal of cellular biochemistry 47 11835393
2003 Upregulation of gp130 and differential activation of STAT and p42/44 MAPK in the rat hippocampus following kainic acid-induced seizures. Brain research. Molecular brain research 46 14597225
2008 Effect of OPC-12759 on EGF receptor activation, p44/p42 MAPK activity, and secretion in conjunctival goblet cells. Experimental eye research 44 18295205
2006 Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase. Experimental eye research 44 16839545
1998 An anchorage-dependent signal distinct from p42/44 MAP kinase activation is required for cell cycle progression. Oncogene 44 9771970
1999 The p42 variant of ETS1 protein rescues defective Fas-induced apoptosis in colon carcinoma cells. Proceedings of the National Academy of Sciences of the United States of America 43 10097131
2003 Angiotensin II activates cholesterol ester hydrolase in bovine adrenal glomerulosa cells through phosphorylation mediated by p42/p44 mitogen-activated protein kinase. Endocrinology 42 12960096
2000 Albumin stimulates p44/p42 extracellular-signal-regulated mitogen-activated protein kinase in opossum kidney proximal tubular cells. Clinical science (London, England : 1979) 42 10677388
2001 CD40 ligation induces macrophage IL-10 and TNF-alpha production: differential use of the PI3K and p42/44 MAPK-pathways. Cytokine 40 11792123
2001 Regulation of VEGF-induced endothelial cell PAF synthesis: role of p42/44 MAPK, p38 MAPK and PI3K pathways. British journal of pharmacology 39 11704645
2006 Rho kinase, myosin-II, and p42/44 MAPK control extracellular matrix-mediated apical bile canalicular lumen morphogenesis in HepG2 cells. Molecular biology of the cell 38 16687572
2000 PKC, p42/p44 MAPK, and p38 MAPK are required for HGF-induced proliferation of H441 cells. American journal of physiology. Lung cellular and molecular physiology 38 11053031
1999 MIP-3alpha induces human eosinophil migration and activation of the mitogen-activated protein kinases (p42/p44 MAPK). Journal of leukocyte biology 38 10534125
2001 Regulation of p42/p44 MAPK and p38 MAPK by the adenosine A(1) receptor in DDT(1)MF-2 cells. European journal of pharmacology 37 11226388
2008 Inhibition of lipopolysaccharide-induced nitric oxide synthesis by nicotine through S6K1-p42/44 MAPK pathway and STAT3 (Ser 727) phosphorylation in Raw 264.7 cells. Cytokine 36 18723372
2009 A(1) adenosine receptor-mediated PKC and p42/p44 MAPK signaling in mouse coronary artery smooth muscle cells. American journal of physiology. Heart and circulatory physiology 35 19592614
2014 Paxillin mediates stretch-induced Rho signaling and endothelial permeability via assembly of paxillin-p42/44MAPK-GEF-H1 complex. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 24706358
2008 Hepatocyte growth factor regulates cyclooxygenase-2 expression via beta-catenin, Akt, and p42/p44 MAPK in human bronchial epithelial cells. American journal of physiology. Lung cellular and molecular physiology 34 18245266
2002 Two transactivation domains of hypoxia-inducible factor-1alpha regulated by the MEK-1/p42/p44 MAPK pathway. Molecules and cells 34 12243358
2005 Reactive oxidant and p42/44 MAP kinase signaling is necessary for mechanical strain-induced proliferation in pulmonary epithelial cells. Journal of applied physiology (Bethesda, Md. : 1985) 33 15890751
2004 Involvement of p42/44 MAPK and RhoA protein in augmentation of ACh-induced bronchial smooth muscle contraction by TNF-alpha in rats. Journal of applied physiology (Bethesda, Md. : 1985) 33 15322069
2003 Oncogenic Ha-Ras transformation modulates the transcription of the CTP:phosphocholine cytidylyltransferase alpha gene via p42/44MAPK and transcription factor Sp3. The Journal of biological chemistry 33 12584202
1998 Inhibition of alanyl aminopeptidase induces MAP-kinase p42/ERK2 in the human T cell line KARPAS-299. Biochemical and biophysical research communications 33 9813136
2011 p38 and p42/44 MAPKs differentially regulate progesterone receptor A and B isoform stabilization. Molecular endocrinology (Baltimore, Md.) 32 21816898
1999 Influenza C virus CM2 protein is produced from a 374-amino-acid protein (P42) by signal peptidase cleavage. Journal of virology 32 9847305
2006 PGE2 stimulates human brain natriuretic peptide expression via EP4 and p42/44 MAPK. American journal of physiology. Heart and circulatory physiology 30 16428339
1999 Distinct roles for p42/p44 and p38 mitogen-activated protein kinases in the induction of IL-2 by IL-1. Cytokine 30 10479400
2007 p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle. American journal of physiology. Lung cellular and molecular physiology 29 17237147
2005 Neuropeptides B and W enhance the growth of human adrenocortical carcinoma-derived NCI-H295 cells by exerting MAPK p42/p44-mediated proliferogenic and antiapoptotic effects. International journal of molecular medicine 29 16273281
2001 Phosphorylation of p42/44(MAPK) by various signal transduction pathways activates cytosolic phospholipase A(2) to variable degrees. The Journal of biological chemistry 28 11390384
2006 Acetaminophen recruits spinal p42/p44 MAPKs and GH/IGF-1 receptors to produce analgesia via the serotonergic system. Molecular pharmacology 27 17088403
2002 Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilization. Biochemical and biophysical research communications 27 11779151
2015 Sphingosine-1-phosphate mediates ICAM-1-dependent monocyte adhesion through p38 MAPK and p42/p44 MAPK-dependent Akt activation. PloS one 26 25734900
2010 AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay. Nucleic acids research 26 20716519
2003 Norepinephrine activates P44 and P42 MAPK in human prostate stromal and smooth muscle cells but not in epithelial cells. The Prostate 26 12858360
1999 p42/p44 mitogen-activated protein kinase activation is involved in prostaglandin F2alpha-induced interleukin-6 synthesis in osteoblasts. Cellular signalling 26 10376804
2024 The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-associated disease. Journal of neurology, neurosurgery, and psychiatry 25 38290838
2014 Systemic delivery of P42 peptide: a new weapon to fight Huntington's disease. Acta neuropathologica communications 25 25091984
2011 Tianeptine potentiates AMPA receptors by activating CaMKII and PKA via the p38, p42/44 MAPK and JNK pathways. Neurochemistry international 24 22056552
1996 Differential long-term regulation of MEK and of p42 MAPK in rat glomerular mesangial cells. The American journal of physiology 24 8772428
2021 The Silence of PSMC6 Inhibits Cell Growth and Metastasis in Lung Adenocarcinoma. BioMed research international 23 34239933
2016 The P42 peptide and Peptide-based therapies for Huntington's disease. Orphanet journal of rare diseases 23 26984770
2015 P42 Ebp1 functions as a tumor suppressor in non-small cell lung cancer. BMB reports 23 24998263