Affinage

PLCB1

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 · UniProt Q9NQ66

Length
1216 aa
Mass
138.6 kDa
Annotated
2026-06-10
26 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLCB1 encodes a ~150 kDa phosphoinositide-specific phospholipase C whose central region constitutes the catalytic domain and whose enzymatic activity was confirmed by reconstitution from cloned cDNA (PMID:2455601); its hydrolysis of plasma membrane PI(4,5)P2 underpins its role as a signaling node coupling lipid metabolism to cytoskeletal and transcriptional programs (PMID:37208557). Through PI3K/AKT signaling, PLCB1 drives epithelial-to-mesenchymal transition via the GSK3β/Snail axis and confers therapy resistance across multiple cancers, an output amplified by physical interaction with PABPC1 and PI3K (PMID:34580062, PMID:37208557). In parallel, PLCB1 remodels the actin cytoskeleton through the RhoA/LIMK/Cofilin pathway to promote migration and invasion (PMID:37208557), and it suppresses Wnt signaling by promoting destruction-complex-independent ubiquitination and proteasomal degradation of β-catenin (PMID:39053384). PLCB1 expression is directly controlled at the transcriptional level by EGR-1 (PMID:25192965) and FOS (PMID:39451071), and is further tuned post-transcriptionally by microRNA networks (miR-1290, miR-7-5p) that modulate its abundance in disease contexts (PMID:39053384, PMID:36611865). In the brain, Plcb1 is required for normal neuronal function, with heterozygous loss altering prefrontal cortex transcriptomes and reducing cue-induced reinstatement of cocaine-seeking (PMID:34635637).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1988 High

    Established that the PLCB1 cDNA encodes a catalytically active phosphoinositide-specific phospholipase C, defining its core biochemical identity and locating the catalytic domain to the central region.

    Evidence cDNA cloning with transient expression in COS-1 cells and homology-based domain assignment

    PMID:2455601

    Open questions at the time
    • No structural model of the catalytic domain
    • Regulation of enzymatic activity not addressed
    • In vivo substrate dynamics not measured
  2. 2014 High

    Resolved how PLCB1 transcription is controlled by mapping its promoter and identifying EGR-1 as a direct upstream activator.

    Evidence 5'-RACE, luciferase reporter deletion constructs, EMSA, and EGR-1 overexpression in multiple cell lines

    PMID:25192965

    Open questions at the time
    • Physiological stimuli driving EGR-1-dependent PLCB1 induction not defined
    • Other promoter regulators not characterized
  3. 2021 Medium

    Connected PLCB1 to oncogenic PI3K/AKT signaling, showing it drives EMT and chemoresistance and physically partners with PABPC1 and PI3K.

    Evidence Co-IP, siRNA/overexpression, transposon in vivo tumorigenesis, and AKT inhibitor rescue in cholangiocarcinoma cells

    PMID:34580062

    Open questions at the time
    • Co-IP interactions lack reciprocal/structural validation
    • Whether catalytic activity is required for AKT activation untested
    • Single tumor type and single lab
  4. 2021 Medium

    Identified HDAC8 as an upstream driver of PLCB1 expression linking epigenetic regulation to MEK inhibitor resistance via AKT.

    Evidence Microarray plus qPCR, siRNA of HDAC8 and PLCB1, HDAC8 inhibitors, and AKT activity assays

    PMID:34064422

    Open questions at the time
    • Mechanism by which HDAC8 regulates the PLCB1 locus not resolved
    • Direct vs indirect transcriptional effect unclear
    • Single lab
  5. 2021 Medium

    Placed PLCB1 in neuronal signaling in vivo, showing heterozygous loss alters prefrontal cortex transcriptomes and addiction-related behavior.

    Evidence Plcb1+/- mouse operant reinstatement paradigm with prefrontal cortex RNA sequencing

    PMID:34635637

    Open questions at the time
    • Molecular link from PLCB1 loss to dopaminergic/LTP pathway changes not mechanistic
    • Cell-type-specific contributions undefined
    • Single lab
  6. 2022 Medium

    Showed PLCB1 is anti-inflammatory in pancreatitis and is post-transcriptionally controlled by an SNHG11/miR-7-5p axis acting through p38MAPK.

    Evidence Dual-luciferase and RIP target validation, overexpression/shRNA, and in vivo acute pancreatitis model

    PMID:36611865

    Open questions at the time
    • How PLCB1 modulates p38MAPK mechanistically unresolved
    • Whether enzymatic activity mediates the protective effect untested
    • Single lab
  7. 2023 Medium

    Defined a dual mechanism in which PLCB1 drives both actin remodeling via RhoA/LIMK/Cofilin and EMT via AKT, tied to its regulation of plasma membrane PI(4,5)P2.

    Evidence siRNA/overexpression with migration/invasion assays and pathway Western blots in gastric cancer cells

    PMID:37208557

    Open questions at the time
    • Direct causal link between PI(4,5)P2 changes and RhoA activation not established
    • No structural or live-imaging validation
    • Single lab
  8. 2024 Medium

    Revealed a non-canonical PLCB1 function: promoting destruction-complex-independent ubiquitination and degradation of β-catenin to suppress Wnt signaling, with miR-1290 as an upstream regulator.

    Evidence Ubiquitination assays, miR-1290 and PLCB1 manipulation, and in vivo glioma model with Wnt inhibitor

    PMID:39053384

    Open questions at the time
    • Identity of the ubiquitin ligase machinery engaged not determined
    • Whether PLCB1 lipase activity is required unclear
    • Single lab
  9. 2024 Medium

    Established FOS as a second direct transcriptional activator of PLCB1, linking PLCB1-driven AKT signaling to radioresistance and suppressed CD8+ T cell antitumor immunity.

    Evidence FOS/PLCB1 knockdown and overexpression, epistasis via PI3K/AKT activator rescue, and CD8+ T cell co-culture in TNBC

    PMID:39451071

    Open questions at the time
    • Direct FOS binding site on PLCB1 promoter not mapped in detail
    • Mechanism linking tumor PLCB1 to T cell function indirect
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved whether PLCB1 catalytic PI(4,5)P2 hydrolysis is mechanistically required for its diverse downstream outputs (AKT, RhoA, β-catenin, p38MAPK), and how a single lipase coordinates these distinct programs in a tissue-specific manner.
  • No experiments separating catalytic from scaffolding functions
  • No structural basis for partner selectivity
  • Tissue-specific signaling logic uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2 GO:0016787 hydrolase activity 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005886 plasma membrane 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3
Partners
PABPC1PI3K

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 PLC-154 (PLCB1) encodes a functional phosphoinositide-specific phospholipase C of ~150 kDa. The central region of PLC-154 shares homology with PLC-148 and was assigned as the putative catalytic domain. Transient expression in COS-1 cells confirmed the encoded protein is enzymatically active. cDNA cloning, transient expression in COS-1 cells, protein sequence analysis, Southern/Northern blotting Cell High 2455601
2014 The PLCB1 promoter was characterized for the first time; transcription initiates from multiple start points, with the main start at nt-235 relative to the translation start. A specific EGR-1 binding site was identified at nt-451/-419, and EGR-1 overexpression increased PLCB1 promoter activity more than 5-fold, placing EGR-1 as a direct transcriptional activator of PLCB1. 5'-RACE, promoter cloning, luciferase reporter assays with deletion constructs, EMSA, EGR-1 overexpression in multiple cell lines European journal of pharmacology High 25192965
2021 PLCB1 activates PI3K/AKT signaling to induce epithelial-to-mesenchymal transition (EMT) in cholangiocarcinoma cells. PABPC1 physically interacts with PLCB1 and PI3K to amplify PLCB1-mediated EMT via the PI3K/AKT/GSK3β/Snail axis. PLCB1-driven AKT activation also confers resistance to gemcitabine/cisplatin, reversible by the AKT inhibitor MK2206. Co-immunoprecipitation (PABPC1–PLCB1–PI3K interaction), transposon-based in vivo tumorigenesis models, siRNA knockdown/overexpression, drug treatment with pathway inhibitor Cancer research Medium 34580062
2021 HDAC8 upregulates PLCB1 expression in MEK1/2 inhibitor-resistant cancer cells, and elevated PLCB1 activates AKT, contributing to resistance. HDAC8 inhibition suppresses PLCB1 expression and re-sensitizes resistant cells to MEK1/2 inhibition; PLCB1 siRNA similarly inhibits AKT activation. Affymetrix microarray followed by qPCR validation, siRNA knockdown of HDAC8 and PLCB1, HDAC8 inhibitors, expression vectors, AKT activity assays Cells Medium 34064422
2023 PLCB1 promotes gastric cancer cell migration and invasion by mediating actin cytoskeletal remodeling via the RhoA/LIMK/Cofilin pathway and by promoting EMT through AKT signaling. PLCB1 regulates the abundance of PI(4,5)P2 at the plasma membrane as part of this mechanism. siRNA knockdown, overexpression, cell migration/invasion assays, Western blot for RhoA/LIMK/Cofilin and AKT pathway components Biochemical genetics Medium 37208557
2024 PLCB1 facilitates proteasomal degradation of β-catenin and active-β-catenin by increasing the proportion of ubiquitinated β-catenin in a destruction complex-independent mechanism. When PLCB1 is downregulated (by miR-1290 induced by increased oxygen), active-β-catenin accumulates and Wnt signaling is boosted, promoting chemoresistance in glioma cells. miR-1290 overexpression/inhibition, PLCB1 knockdown/overexpression, ubiquitination assays, Western blot for β-catenin, in vivo glioma mouse model, WNT974 pharmacological inhibition Drug resistance updates Medium 39053384
2024 The FOS transcription factor directly promotes PLCB1 transcription, and the resulting PLCB1 activates PI3K/AKT signaling to induce radioresistance and weaken CD8+ T cell antitumor effects in triple-negative breast cancer. FOS knockdown phenocopies PLCB1 knockdown, and PI3K/AKT activator or PLCB1 overexpression rescues the phenotype after PLCB1/FOS depletion. PLCB1 and FOS siRNA knockdown, overexpression, PI3K/AKT activator rescue experiments, colony formation, apoptosis, tumorigenesis in mice, CD8+ T cell co-culture assays Molecular carcinogenesis Medium 39451071
2021 Plcb1 heterozygous knockout mice show reduced cue-induced reinstatement of cocaine-seeking behavior after extinction, with transcriptomic alterations in the medial prefrontal cortex related to dopaminergic synapse and long-term potentiation pathways. These mice also showed increased anxiety and impaired short-term memory. Plcb1+/- mouse model, operant self-administration and reinstatement paradigm, RNA sequencing of medial prefrontal cortex Translational psychiatry Medium 34635637
2022 PLCB1 overexpression abrogated caerulein-induced inflammatory damage in pancreatic cells. SNHG11 acts as a sponge for miR-7-5p, thereby upregulating PLCB1, and this SNHG11/miR-7-5p/PLCB1 axis inhibits acute pancreatitis progression by participating in the p38MAPK signaling pathway. Dual-luciferase reporter assay and RIP assay (miR-7-5p–PLCB1 and miR-7-5p–SNHG11 interaction), PLCB1 overexpression/shRNA, in vivo AP model, p38MAPK pathway readouts Cells Medium 36611865

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Determination of the primary structure of PLC-154 demonstrates diversity of phosphoinositide-specific phospholipase C activities. Cell 145 2455601
2021 A PLCB1-PI3K-AKT Signaling Axis Activates EMT to Promote Cholangiocarcinoma Progression. Cancer research 88 34580062
2012 Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy. Epilepsia 70 22690784
2012 Deletion of PLCB1 gene in schizophrenia-affected patients. Journal of cellular and molecular medicine 58 22507702
2015 Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan. Scientific reports 33 26434682
2019 MicroRNA-124 inhibits colorectal cancer cell proliferation and suppresses tumor growth by interacting with PLCB1 and regulating Wnt/β-catenin signaling pathway. European review for medical and pharmacological sciences 30 30657554
2024 Lnc-PLCB1 is stabilized by METTL14 induced m6A modification and inhibits Helicobacter pylori mediated gastric cancer by destabilizing DDX21. Cancer letters 27 38387756
2018 Down-regulation of circ-PRKCI inhibits cell migration and proliferation in Hirschsprung disease by suppressing the expression of miR-1324 target PLCB1. Cell cycle (Georgetown, Tex.) 23 29895226
2014 Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum. Developmental medicine and child neurology 20 24684524
2023 PLCB1 Enhances Cell Migration and Invasion in Gastric Cancer Via Regulating Actin Cytoskeletal Remodeling and Epithelial-Mesenchymal Transition. Biochemical genetics 15 37208557
2022 Effect of SNHG11/miR-7-5p/PLCB1 Axis on Acute Pancreatitis through Inhibiting p38MAPK Pathway. Cells 15 36611865
2021 HDAC8 Activates AKT through Upregulating PLCB1 and Suppressing DESC1 Expression in MEK1/2 Inhibition-Resistant Cells. Cells 14 34064422
2020 Three novel patients with epileptic encephalopathy due to biallelic mutations in the PLCB1 gene. Clinical genetics 13 31883110
2017 Association of the PLCB1 gene with drug dependence. Scientific reports 12 28860459
2024 Increased oxygen stimulation promotes chemoresistance and phenotype shifting through PLCB1 in gliomas. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 11 39053384
2021 Circ_0091579 Serves as a Tumor-Promoting Factor in Hepatocellular Carcinoma Through miR-1225-5p/PLCB1 Axis. Digestive diseases and sciences 11 33559088
2023 Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency. Frontiers in molecular neuroscience 8 37063368
2014 Characterization of the PLCB1 promoter and regulation by early growth response transcription factor EGR-1. European journal of pharmacology 7 25192965
2024 FOS-Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8+ T Cells in Triple-Negative Breast Cancer. Molecular carcinogenesis 6 39451071
2024 LncRNA AC100826.1 regulated PLCB1 to promote progression in non-small cell lung cancer. Thoracic cancer 4 38778543
2021 Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice. Translational psychiatry 4 34635637
2023 Refractory Jeavons Syndrome from Birth Symptomatic to PLCB1 Mutation. Child neurology open 3 37441061
2024 Single-Cell Transcriptomic and Targeted Genomic Profiling Adjusted for Inflammation and Therapy Bias Reveal CRTAM and PLCB1 as Novel Hub Genes for Anti-Tumor Necrosis Factor Alpha Therapy Response in Crohn's Disease. Pharmaceutics 2 38931955
2024 Elucidating the Role of circTIAM1 in Guangling Large-Tailed Sheep Adipocyte Proliferation and Differentiation via the miR-485-3p/PLCB1 Pathway. International journal of molecular sciences 1 38731807
2021 Investigation of high correlation with carcass traits of SNPs of the PLCB1, C/EBPα, and TDRKH genes and the combinations of SNPs using the MDR method in the Hanwoo. Genes & genomics 1 34129193
2024 Corrigendum to "Refractory Jeavons Syndrome from Birth Symptomatic to PLCB1 Mutation". Child neurology open 0 39219848

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