Affinage

PRIMA1

Proline-rich membrane anchor 1 · UniProt Q86XR5

Length
153 aa
Mass
16.7 kDa
Annotated
2026-06-10
100 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRIMA1 encodes PRiMA (proline-rich membrane anchor), the dedicated transmembrane scaffold that organizes acetylcholinesterase (AChE) catalytic subunits into G4 tetramers and anchors them at the cell surface of brain and muscle membranes (PMID:11804574). Assembly is driven by PRiMA's proline-rich extracellular motif (PRAD), which is sufficient to nucleate a hetero-oligomer of four cholinesterase T-subunits and direct their secretion or membrane retention; truncation within this motif instead diverts associated subunits to intracellular degradation (PMID:17158452), and tetramer formation depends on the C-terminal t-peptides of the cholinesterase subunits (PMID:20566626). PRiMA-linked tetramers are targeted to membrane lipid rafts through a CRAC cholesterol-recognition motif at the transmembrane–cytoplasmic junction, with the longer PRiMA I isoform conferring stronger raft association (PMID:20147288), while N-glycosylation of the AChE subunit is required for full catalytic activity and for trafficking beyond the endoplasmic reticulum but is dispensable for oligomerization (PMID:21795704). PRiMA is expressed predominantly in cholinergic neurons and is the limiting factor for assembly of the major brain AChE form (PMID:14622217); its transcription is induced during neuronal differentiation through a Raf/MEK/ERK pathway (PMID:19368807) and by cAMP signaling (PMID:18514641), and the complex is regulated at the neuromuscular junction in a motor-neuron-dependent manner (PMID:19490106). The complex is further controlled post-translationally by presenilin-1/γ-secretase, which cleaves PRiMA to release a nuclear-localized C-terminal fragment and modulates the surface pool of AChE (PMID:24612677). Loss-of-function mutation of PRIMA1 causes autosomal recessive nocturnal frontal lobe epilepsy with intellectual disability, with accumulation of synaptic acetylcholine and elevated cholinergic tone as the disease mechanism (PMID:26339676).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Established the molecular identity of the long-sought membrane anchor for brain and muscle AChE, answering how soluble catalytic subunits become surface-tethered tetramers.

    Evidence Molecular cloning and reconstitution in transfected COS cells, with confirmation in native neural membranes

    PMID:11804574

    Open questions at the time
    • Structure of the PRiMA–AChE complex not resolved
    • Stoichiometric and kinetic details of assembly not defined at the time
  2. 2003 High

    Defined the cellular distribution and rate-limiting role of PRiMA, showing its expression in cholinergic neurons controls how much of the major brain AChE form is produced, and revealed splice variant diversity.

    Evidence In situ hybridization, cholinesterase activity assays of molecular forms, and RT-PCR of splice variants in mouse and human tissue

    PMID:14622217

    Open questions at the time
    • Functional distinction between PRiMA I and II not established here
    • Mechanism limiting complex production not detailed
  3. 2006 High

    Mapped the assembly determinant to the proline-rich PRAD motif and showed it is both sufficient for tetramer formation and required to prevent degradation of unassembled subunits.

    Evidence Deletion and point mutagenesis of PRiMA in transfected COS cells with secreted/membrane AChE activity readouts

    PMID:17158452

    Open questions at the time
    • Atomic details of PRAD–t-peptide interaction not resolved
    • Quality-control machinery degrading mis-assembled subunits not identified
  4. 2008 High

    Distinguished PRiMA-based assembly from ColQ-based assembly and identified the cysteines that disulfide-link the tetramer, clarifying complex architecture.

    Evidence PRiMA/ColQ chimeras and cysteine mutants in COS cells, reducing/non-reducing SDS-PAGE, native brain analysis

    PMID:18511416

    Open questions at the time
    • Functional consequence of light- vs heavy-dimer predominance unknown
    • No structural model of the disulfide network
  5. 2008 Medium

    Identified a regulatory input controlling assembly, showing cAMP signaling coordinately upregulates PRiMA and AChE to increase G4 levels.

    Evidence Bt2-cAMP/forskolin treatment of PC12 cells with RT-PCR, activity assays, and sucrose gradients

    PMID:18514641

    Open questions at the time
    • Transcription factors mediating cAMP induction not identified
    • Single cell-line model
  6. 2009 High

    Showed PRiMA transcription is developmentally induced through Raf/MEK/ERK signaling, linking neuronal differentiation cues to cholinergic enzyme assembly.

    Evidence Promoter-luciferase reporters, MEK inhibition (U0126), and active-Raf overexpression in cortical neurons

    PMID:19368807

    Open questions at the time
    • Direct promoter-binding transcription factors not defined
    • Crosstalk with cAMP pathway not resolved
  7. 2009 High

    Demonstrated motor-neuron-dependent regulation of PRiMA-linked G4 AChE at the neuromuscular junction.

    Evidence Western blot, ELISA, immunohistochemistry, and denervation in rat muscle and spinal cord

    PMID:19490106

    Open questions at the time
    • Neuronal signals driving muscle PRiMA expression not identified
    • Relative contributions of nerve vs muscle pools not quantified
  8. 2009 Medium

    Characterized the PRiMA II splice variant and showed both isoforms support G4 assembly, with isoform expression tracking muscle fiber type.

    Evidence RT-PCR, bioinformatics, co-expression in cultured cells, and fiber-type analysis in chicken

    PMID:19539694

    Open questions at the time
    • Functional advantage of isoform-specific cytoplasmic tails unclear
    • Data from chicken; mammalian relevance partial
  9. 2010 High

    Defined the lipid-raft targeting mechanism, localizing PRiMA-linked tetramers to rafts via a CRAC cholesterol-binding motif and the cytoplasmic domain.

    Evidence Detergent-resistant membrane fractionation of brain and NG108-15 cells with CRAC motif mutagenesis and isoform comparison

    PMID:20147288

    Open questions at the time
    • Functional role of raft residence for cholinergic signaling not established
    • Direct cholesterol binding not biophysically measured
  10. 2010 High

    Established subunit assembly rules, showing tetramers build from cholinesterase homodimers via catalytic domains and t-peptides, and that natural AChE–BChE hybrids form.

    Evidence Co-transfection of AChET/BChET mutants with PRiMA, non-reducing SDS-PAGE, sedimentation, and chicken brain analysis

    PMID:20566626

    Open questions at the time
    • Physiological role of hybrid tetramers unknown
    • Determinants of homo- vs heterodimer preference not fully defined
  11. 2011 High

    Separated the requirements for catalytic activity and assembly/trafficking, showing AChE N-glycosylation is needed for activity and ER exit but not for oligomerization.

    Evidence Glycosylation-null AChET mutants co-expressed with PRiMA in HEK293T cells with kinetic, fractionation, and immunofluorescence readouts

    PMID:21795704

    Open questions at the time
    • Glycan-dependent ER export checkpoint not mechanistically identified
    • Whether PRiMA itself is glycosylation-dependent not addressed
  12. 2014 Medium

    Identified post-translational proteolytic regulation, showing γ-secretase/PS1 cleaves PRiMA to release a nuclear C-terminal fragment and controls the surface AChE pool.

    Evidence DAPT treatment of CHO cells, immunofluorescence of the C-terminal fragment, and PS1 conditional KO raft analysis

    PMID:24612677

    Open questions at the time
    • Function of the nuclear PRiMA fragment unknown
    • Cleavage site and physiological trigger not defined
    • Single-lab finding
  13. 2015 Medium

    Connected PRIMA1 loss of function to human disease, establishing it as a cause of autosomal recessive nocturnal frontal lobe epilepsy via cholinergic excess.

    Evidence Whole-exome sequencing, linkage, minigene splicing assay of a c.93+2T>C variant, referenced to KO mouse phenotype

    PMID:26339676

    Open questions at the time
    • Disease mechanism inferred from mouse rather than patient tissue
    • Single family
    • Genotype-phenotype range not defined
  14. 2015 Medium

    Linked chronic loss of PRiMA-anchored AChE to downstream cholinergic circuit dysfunction, showing M2 autoreceptor failure in vivo.

    Evidence PRiMA KO mouse with striatal/hippocampal microdialysis and muscarinic pharmacological challenge

    PMID:26506622

    Open questions at the time
    • Whether M2 dysfunction is cause or consequence of elevated ACh not separated
    • Receptor-level molecular changes not directly measured

Open questions

Synthesis pass · forward-looking unresolved questions
  • The function of the γ-secretase-generated nuclear PRiMA fragment and whether PRiMA has signaling roles independent of AChE anchoring remain unresolved.
  • No identified nuclear targets or transcriptional effects of the C-terminal fragment
  • No structural model of the PRiMA–AChE complex
  • AChE-independent functions of PRiMA untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Partners
ACHEBCHEPSEN1
Complex memberships
PRiMA-AChE G4 tetramer

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PRiMA (proline-rich membrane anchor, encoded by PRIMA1) is the membrane anchor of acetylcholinesterase (AChE) in mammalian brain and muscle cell membranes. PRiMA organizes AChE into tetramers and anchors them at the cell surface of transfected cells; endogenous AChE in neural cell membranes is anchored through its interaction with PRiMA. Molecular cloning, transfection of COS cells, biochemical fractionation, and demonstration of AChE tetramer formation at the cell surface Neuron High 11804574
2003 PRiMA is expressed predominantly in cholinergic neurons in the mouse brain, and its expression level is a limiting factor for production of the AChET–PRiMA complex (the major AChE component in brain). PRiMA exists as two alternative splice variants (PRiMA I and PRiMA II) differing in their cytoplasmic regions in both mouse and human. In situ hybridization, cholinesterase activity assays of molecular forms across brain structures, RT-PCR characterization of splice variants The European journal of neuroscience High 14622217
2006 The proline-rich extracellular motif of PRiMA (specifically the peptidic motif RP4LP10RL) is sufficient to induce assembly of a hetero-oligomeric complex with four AChET subunits and their secretion. Short PRiMA mutants truncated within the proline-rich motif cause intracellular degradation of associated AChE subunits rather than tetramer formation. Deletion and point-mutation analysis of PRiMA expressed in transfected COS cells, measurement of secreted and membrane-bound AChE activity The Journal of biological chemistry High 17158452
2008 PRiMA associates differently with AChE than ColQ does: in complexes formed with the PRAD of PRiMA, light (non-disulfide-linked) AChE dimers predominate, whereas heavy (disulfide-linked) dimers are rare, in contrast to ColQ-linked complexes. PRiMA has four cysteines upstream of its PRAD that can disulfide-bond all four AChE subunits. Transfection of COS cells with PRiMA/ColQ chimeras and cysteine mutants, SDS-PAGE under reducing/non-reducing conditions, analysis of native brain AChE complexes The Journal of biological chemistry High 18511416
2009 PRiMA expression in cortical neurons is transcriptionally upregulated during neuronal differentiation via a MAP kinase (Raf/MEK/ERK)-dependent signaling pathway. Inhibition of MEK with U0126 blocks both PRiMA transcript induction and PRiMA promoter-driven luciferase activity. Overexpression of activated Raf induces both PRiMA and AChET transcripts. RT-PCR, promoter-luciferase reporter assays in cortical neurons, pharmacological MEK inhibition (U0126), overexpression of active Raf mutant Brain research High 19368807
2009 PRiMA-linked G4 AChE is present at vertebrate neuromuscular junctions (NMJs) and is contributed by both motor neurons (spinal cord) and muscle. After denervation, expression of PRiMA, AChET, and G4 AChE decreases markedly in spinal cord and in fast- and slow-twitch muscles, indicating motor neuron–dependent regulation of this complex at the NMJ. Western blot, ELISA, immunohistochemistry in developing rat muscle and spinal cord, denervation experiments The FEBS journal High 19490106
2010 PRiMA-linked AChE tetramers are localized in membrane lipid rafts of neuronal cells, and this raft association depends on a cholesterol recognition/interaction amino acid consensus (CRAC) motif at the junction of the transmembrane and cytoplasmic domains of PRiMA. The longer PRiMA I isoform confers stronger raft association than PRiMA II, implicating the cytoplasmic domain in stabilizing raft localization. Cold Triton X-100 extraction/sucrose gradient fractionation of rat brain and transfected NG108-15 cells, CRAC motif mutation analysis, developmental fractionation time-course The Journal of biological chemistry High 20147288
2010 PRiMA-linked AChE tetramers assemble from AChET and BChET homodimers (not heterodimers); dimer formation depends on catalytic domains and tetramer assembly requires the C-terminal t-peptides of cholinesterase subunits. Hybrid AChE–BChE PRiMA-linked tetramers occur naturally in chicken brain and increase during development. Co-transfection with AChET/BChET mutants and PRiMA in cultured cells, non-reducing SDS-PAGE, sucrose gradient sedimentation, Western blot of chicken brain The Journal of biological chemistry High 20566626
2011 N-linked glycosylation of AChET is required for full enzymatic activity of PRiMA-linked AChE tetramers but is not required for oligomerization. Glycan-depleted PRiMA-linked G4 AChE tetramers assemble in the endoplasmic reticulum but are not transported to the Golgi or plasma membrane. Site-directed mutagenesis of all N-glycosylation sites in AChET expressed with PRiMA in HEK293T cells, kinetic analysis (Km), subcellular fractionation, immunofluorescence The Journal of biological chemistry High 21795704
2014 Presenilin-1 (PS1)/γ-secretase cleaves PRiMA, generating a C-terminal PRiMA fragment that is detectable in the nucleus. Inhibition of γ-secretase increases the level of PRiMA-linked AChE at the cell surface. The proportion of raft-residing AChE–PRiMA is altered in a PS1 conditional knockout mouse. γ-secretase inhibitor (DAPT) treatment of CHO cells overexpressing PRiMA and AChE, immunofluorescence detection of C-terminal PRiMA fragment, analysis of PS1 conditional KO mouse raft fractions Neurobiology of aging Medium 24612677
2008 cAMP-dependent signaling (stimulated by dibutyryl-cAMP and forskolin) upregulates both AChET and PRiMA I mRNA expression in PC12 cells and increases G1 and G4 AChE isoforms, indicating that PRiMA-linked G4 AChE assembly is regulated by a cAMP-dependent pathway. Pharmacological treatment of PC12 cells with Bt2-cAMP/forskolin, RT-PCR, AChE activity measurement, sucrose density gradient sedimentation Chemico-biological interactions Medium 18514641
2015 A homozygous splice-site mutation (c.93+2T>C) in PRIMA1 causes skipping of the first coding exon (demonstrated by minigene assay), effectively creating a PRIMA1 knockout, and segregates with autosomal recessive nocturnal frontal lobe epilepsy and intellectual disability in a human family. Consistent with PRiMA knockout mouse data showing AChE reduction and acetylcholine accumulation, loss of PRIMA1 leads to enhanced cholinergic tone as the likely disease mechanism. Whole-exome sequencing, linkage analysis, minigene splicing assay to demonstrate exon skipping, reference to PRiMA KO mouse phenotype Annals of clinical and translational neurology Medium 26339676
2015 In PRiMA knockout mice, which develop severely reduced AChE activity and chronically elevated extracellular acetylcholine, muscarinic M2 autoreceptors are dysfunctional and fail to reduce ACh release in vivo, likely due to receptor downregulation and/or loss of receptor-effector coupling caused by chronic high ACh. PRiMA KO mouse model, in vivo microdialysis of striatal and hippocampal ACh, pharmacological challenge with oxotremorine (M2 agonist) and scopolamine (antagonist) PloS one Medium 26506622
2009 A second splice variant of PRiMA (PRiMA II) with a distinct 26-amino-acid cytoplasmic C-terminus exists in chicken. Both chicken PRiMA I and PRiMA II can organize G4 AChE formation when co-expressed with AChET in cultured cells. PRiMA I expression is higher in slow-twitch than fast-twitch chicken muscle, suggesting fiber-type-specific regulation of G4 AChE. RT-PCR, bioinformatic analysis, co-expression in cultured cells, fiber-type specific expression analysis Neuroscience letters Medium 19539694

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer cell 493 19411067
2005 PRIMA-1(MET) synergizes with cisplatin to induce tumor cell apoptosis. Oncogene 214 15735745
2002 PRiMA: the membrane anchor of acetylcholinesterase in the brain. Neuron 208 11804574
2021 Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters. International journal of molecular sciences 183 33946854
2011 Positron emission tomography-computed tomography (PET-CT) after induction therapy is highly predictive of patient outcome in follicular lymphoma: analysis of PET-CT in a subset of PRIMA trial participants. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 157 21747087
2016 Risk Factors and Outcomes for Patients With Follicular Lymphoma Who Had Histologic Transformation After Response to First-Line Immunochemotherapy in the PRIMA Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 155 27298402
2013 APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase. Cell death & disease 148 24157875
2002 Mutant p53-dependent growth suppression distinguishes PRIMA-1 from known anticancer drugs: a statistical analysis of information in the National Cancer Institute database. Carcinogenesis 144 12507923
2014 PRIMA-1Met induces myeloma cell death independent of p53 by impairing the GSH/ROS balance. Blood 137 25006124
2011 PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53. Clinical cancer research : an official journal of the American Association for Cancer Research 117 21415220
2019 Synergistic effects of PRIMA-1Met (APR-246) and 5-azacitidine in TP53-mutated myelodysplastic syndromes and acute myeloid leukemia. Haematologica 116 31488557
2017 PRIMA-1 and PRIMA-1Met (APR-246): From Mutant/Wild Type p53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies. Cancers 104 29258181
2017 Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples. Epigenetics 96 28753106
2008 Sexual dysfunction: the 'prima ballerina' of hypertension-related quality-of-life complications. Journal of hypertension 90 18854743
2009 Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene 85 19946333
2013 PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by induction of p73 and Noxa. Molecular cancer therapeutics 79 24030633
2019 p53 reactivation with induction of massive apoptosis-1 (PRIMA-1) inhibits amyloid aggregation of mutant p53 in cancer cells. The Journal of biological chemistry 77 30602570
2012 Mesotoga prima gen. nov., sp. nov., the first described mesophilic species of the Thermotogales. Extremophiles : life under extreme conditions 73 22411358
2009 PRIMA-1 inhibits growth of breast cancer cells by re-activating mutant p53 protein. International journal of oncology 63 19787255
2013 Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET. Proceedings of the National Academy of Sciences of the United States of America 62 23355677
2015 Stimulation of suicidal erythrocyte death by PRIMA-1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 61 25614142
2016 APR-246 (PRIMA-1(MET)) strongly synergizes with AZD2281 (olaparib) induced PARP inhibition to induce apoptosis in non-small cell lung cancer cell lines. Cancer letters 55 26975633
2014 PRIMA-1, a mutant p53 reactivator, induces apoptosis and enhances chemotherapeutic cytotoxicity in pancreatic cancer cell lines. Investigational new drugs 55 24838627
2004 Effects of PRIMA-1 on chronic lymphocytic leukaemia cells with and without hemizygous p53 deletion. British journal of haematology 55 15491287
2005 Proteomic identification of heat shock protein 90 as a candidate target for p53 mutation reactivation by PRIMA-1 in breast cancer cells. Breast cancer research : BCR 53 16168122
2010 PRIMA-1(MET)/APR-246 targets mutant forms of p53 family members p63 and p73. Oncogene 52 20818419
2016 p53 Reactivation by PRIMA-1(Met) (APR-246) sensitises (V600E/K)BRAF melanoma to vemurafenib. European journal of cancer (Oxford, England : 1990) 51 26790143
2015 DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer. BMC cancer 51 26482433
2006 PRIMA-1 induces apoptosis in acute myeloid leukaemia cells with p53 gene deletion. British journal of haematology 51 16398657
2008 PRIMA-1MET induces mitochondrial apoptosis through activation of caspase-2. Oncogene 50 18663359
2005 Selective induction of apoptosis in mutant p53 premalignant and malignant cancer cells by PRIMA-1 through the c-Jun-NH2-kinase pathway. Molecular cancer therapeutics 49 15956247
2014 Is the neutrophil a 'prima donna' in the procoagulant process during sepsis? Critical care (London, England) 48 25041721
2011 PRIMA-1Met/APR-246 induces wild-type p53-dependent suppression of malignant melanoma tumor growth in 3D culture and in vivo. Cell cycle (Georgetown, Tex.) 48 21239882
2010 Targeting acetylcholinesterase to membrane rafts: a function mediated by the proline-rich membrane anchor (PRiMA) in neurons. The Journal of biological chemistry 48 20147288
2012 Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms. Blood 46 22885164
2015 PRIMA-1met (APR-246) inhibits growth of colorectal cancer cells with different p53 status through distinct mechanisms. Oncotarget 45 26452133
2011 The assembly of proline-rich membrane anchor (PRiMA)-linked acetylcholinesterase enzyme: glycosylation is required for enzymatic activity but not for oligomerization. The Journal of biological chemistry 44 21795704
2011 Reactivation of p53 mutants by prima-1 [corrected] in thyroid cancer cells. International journal of cancer 43 21647879
2013 APR-246/PRIMA-1(MET) rescues epidermal differentiation in skin keratinocytes derived from EEC syndrome patients with p63 mutations. Proceedings of the National Academy of Sciences of the United States of America 37 23355676
2013 Variability in functional p53 reactivation by PRIMA-1(Met)/APR-246 in Ewing sarcoma. British journal of cancer 37 24129240
2003 Expression of PRiMA in the mouse brain: membrane anchoring and accumulation of 'tailed' acetylcholinesterase. The European journal of neuroscience 37 14622217
2021 Antitumor Effects of PRIMA-1 and PRIMA-1Met (APR246) in Hematological Malignancies: Still a Mutant P53-Dependent Affair? Cells 36 33430525
2019 Adjuvant therapy of cytomegalovirus IgM + ve associated biliary atresia: Prima facie evidence of effect. Journal of pediatric surgery 36 30772005
2016 Sensitivity to PRIMA-1MET is associated with decreased MGMT in human glioblastoma cells and glioblastoma stem cells irrespective of p53 status. Oncotarget 35 27533246
2016 PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells. Oncology reports 33 26986846
2012 Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution. BMC genomics 32 22296923
2006 PRIMA-1 induces apoptosis by inhibiting JNK signaling but promoting the activation of Bax. Biochemical and biophysical research communications 31 17113036
2015 Silencing of CD24 Enhances the PRIMA-1-Induced Restoration of Mutant p53 in Prostate Cancer Cells. Clinical cancer research : an official journal of the American Association for Cancer Research 29 26712693
2016 MiRNA-29a as a tumor suppressor mediates PRIMA-1Met-induced anti-myeloma activity by targeting c-Myc. Oncotarget 28 26771839
2008 PRIMA-1 synergizes with adriamycin to induce cell death in non-small cell lung cancer cells. Journal of cellular biochemistry 28 18442053
1980 Naturally occurring alterations of cortical layers surrounding the fissura prima of rat cerebellum. The Journal of comparative neurology 28 7410606
2015 PRIMA-1(MET) induces death in soft-tissue sarcomas cell independent of p53. BMC cancer 27 26463477
2014 PRIMA-1, a mutant p53 reactivator, restores the sensitivity of TP53 mutant-type thyroid cancer cells to the histone methylation inhibitor 3-Deazaneplanocin A. The Journal of clinical endocrinology and metabolism 27 24512488
2009 Transcriptional regulation of proline-rich membrane anchor (PRiMA) of globular form acetylcholinesterase in neuron: an inductive effect of neuron differentiation. Brain research 27 19368807
2016 PRIMA-1 targets the vulnerability of multiple myeloma of deregulated protein homeostasis through the perturbation of ER stress via p73 demethylation. Oncotarget 26 27533450
2012 Hypoxia, Mn-SOD and H(2)O(2) regulate p53 reactivation and PRIMA-1 toxicity irrespective of p53 status in human breast cancer cells. Biochemical pharmacology 26 22982566
2007 In vitro and in vivo cytotoxic effects of PRIMA-1 on hepatocellular carcinoma cells expressing mutant p53ser249. Carcinogenesis 26 18048389
2006 Assembly of acetylcholinesterase tetramers by peptidic motifs from the proline-rich membrane anchor, PRiMA: competition between degradation and secretion pathways of heteromeric complexes. The Journal of biological chemistry 26 17158452
2013 PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53. Biochimica et biophysica acta 25 23545415
2011 Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model. Clinics (Sao Paulo, Brazil) 24 22189739
2019 PRIMA-1MET-induced neuroblastoma cell death is modulated by p53 and mycn through glutathione level. Journal of experimental & clinical cancer research : CR 23 30755224
2010 MicroRNA-34a is an important component of PRIMA-1-induced apoptotic network in human lung cancer cells. International journal of cancer 23 19921694
2009 Restricted localization of proline-rich membrane anchor (PRiMA) of globular form acetylcholinesterase at the neuromuscular junctions--contribution and expression from motor neurons. The FEBS journal 23 19490106
2006 Modulation of p53 transcriptional activity by PRIMA-1 and Pifithrin-alpha on staurosporine-induced apoptosis of wild-type and mutated p53 epithelial cells. Apoptosis : an international journal on programmed cell death 23 16554962
2015 PRIMA-1Met induces apoptosis in Waldenström's Macroglobulinemia cells independent of p53. Cancer biology & therapy 22 25803193
2017 PRIMA-1 induces p53-mediated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation. Cancer science 21 29168598
2010 PRiMA directs a restricted localization of tetrameric AChE at synapses. Chemico-biological interactions 21 20178777
2010 PRIMA-1 cytotoxicity correlates with nucleolar localization and degradation of mutant p53 in breast cancer cells. Biochemical and biophysical research communications 21 20946886
2020 Improvement of epidermal covering on AEC patients with severe skin erosions by PRIMA-1MET/APR-246. Cell death & disease 20 31949132
2016 Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder. International journal of molecular sciences 20 26742039
2010 The PRiMA-linked cholinesterase tetramers are assembled from homodimers: hybrid molecules composed of acetylcholinesterase and butyrylcholinesterase dimers are up-regulated during development of chicken brain. The Journal of biological chemistry 20 20566626
2015 PRIMA1 mutation: a new cause of nocturnal frontal lobe epilepsy. Annals of clinical and translational neurology 19 26339676
2013 PRIMA-1 increases cisplatin sensitivity in chemoresistant ovarian cancer cells with p53 mutation: a requirement for Akt down-regulation. Journal of ovarian research 19 23351152
2016 Autoantibodies to neuronal antigens in children with focal epilepsy and no prima facie signs of encephalitis. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 18 27056280
2016 PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK. Oncotarget 18 27806324
2012 Genome sequence of the mesophilic Thermotogales bacterium Mesotoga prima MesG1.Ag.4.2 reveals the largest Thermotogales genome to date. Genome biology and evolution 18 22798451
2006 Effects of PRIMA-1 on wild-type L1210 cells expressing mutant p53 and drug-resistant L1210 cells lacking expression of p53: necrosis vs. apoptosis. Anticancer research 18 16619536
2013 Chemopreventive effects of the p53-modulating agents CP-31398 and Prima-1 in tobacco carcinogen-induced lung tumorigenesis in A/J mice. Neoplasia (New York, N.Y.) 17 24027427
2006 Expression proteomics to p53 mutation reactivation with PRIMA-1 in breast cancer cells. Biochemical and biophysical research communications 16 16970918
2004 Prima facie evidence that a phytocystatin for transgenic plant resistance to nematodes is not a toxic risk in the human diet. The Journal of nutrition 16 14747684
2019 Targeting Oxidative Stress With Auranofin or Prima-1Met to Circumvent p53 or Bax/Bak Deficiency in Myeloma Cells. Frontiers in oncology 15 30895171
2018 Synergistic Antitumor Effect of BKM120 with Prima-1Met Via Inhibiting PI3K/AKT/mTOR and CPSF4/hTERT Signaling and Reactivating Mutant P53. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 15 29495002
2008 Acetylcholinesterase associates differently with its anchoring proteins ColQ and PRiMA. The Journal of biological chemistry 15 18511416
2016 APR-246/PRIMA-1Met Inhibits and Reverses Squamous Metaplasia in Human Conjunctival Epithelium. Investigative ophthalmology & visual science 14 26868746
2020 Co-Delivery of 131 I and Prima-1 by Self-Assembled CD44-Targeted Nanoparticles for Anaplastic Thyroid Carcinoma Theranostics. Advanced healthcare materials 12 33326188
2014 PRIMA-1 selectively induces global DNA demethylation in p53 mutant-type thyroid cancer cells. Journal of biomedical nanotechnology 12 24804545
2014 Characterizing the sphingomyelinase pathway triggered by PRIMA-1 derivatives in lung cancer cells with differing p53 status. Anticancer research 12 24982331
2009 Expression and Localization of PRiMA-linked globular form acetylcholinesterase in vertebrate neuromuscular junctions. Journal of molecular neuroscience : MN 12 19680821
2023 PRIMA-1 inhibits Y220C p53 amyloid aggregation and synergizes with cisplatin in hepatocellular carcinoma. Frontiers in molecular biosciences 11 37101558
2015 Dysfunctional Presynaptic M2 Receptors in the Presence of Chronically High Acetylcholine Levels: Data from the PRiMA Knockout Mouse. PloS one 11 26506622
2021 PRIMA: a rapid and cost-effective genotyping method to detect single-nucleotide differences using probe-induced heteroduplexes. Scientific reports 10 34689172
2017 PRIMA-1 induces caspase-mediated apoptosis in acute promyelocytic leukemia NB4 cells by inhibition of nuclear factor-κB and downregulation of Bcl-2, XIAP, and c-Myc. Anti-cancer drugs 10 27548348
2013 Prima-1 induces apoptosis in bladder cancer cell lines by activating p53. Clinics (Sao Paulo, Brazil) 10 23644847
2023 In silico and in vitro investigation of dual targeting Prima-1MET as precision therapeutic against lungs cancer. Journal of biomolecular structure & dynamics 9 37272907
2022 p53 reactivating small molecule PRIMA‑1MET/APR‑246 regulates genomic instability in MDA‑MB‑231 cells. Oncology reports 9 35234267
2014 Presenilin-1 influences processing of the acetylcholinesterase membrane anchor PRiMA. Neurobiology of aging 9 24612677
2009 A new variant of proline-rich membrane anchor (PRiMA) of acetylcholinesterase in chicken: expression in different muscle fiber types. Neuroscience letters 9 19539694
2008 Regulation of PRiMA-linked G(4) AChE by a cAMP-dependent signaling pathway in cultured rat pheochromocyoma PC12 cells. Chemico-biological interactions 9 18514641
2022 Analysing the protection from respiratory tract infections and allergic diseases early in life by human milk components: the PRIMA birth cohort. BMC infectious diseases 8 35164699
2002 The malformation of the cerebellar fissura prima: a tool for studying histogenetic processes. Cerebellum (London, England) 8 12882363

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