Affinage

BOP1

Ribosome biogenesis protein BOP1 · UniProt Q14137

Length
746 aa
Mass
83.6 kDa
Annotated
2026-06-09
25 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BOP1 is a conserved WD40-repeat nucleolar protein that serves as the integral scaffold of the trimeric PeBoW complex (BOP1–Pes1–WDR12) and drives maturation of the large (60S) ribosomal subunit (PMID:10891491, PMID:16043514, PMID:17353269). It cosediments with pre-ribosomal particles containing the 32S rRNA precursor and is required for pre-rRNA processing at four distinct sites within ITS1, ITS2, and the 3' external spacer, generating mature 28S and 5.8S rRNAs; dominant-negative or antisense disruption blocks the 36S→32S conversion and 32S processing, depleting cytosolic 60S subunits and arresting cells in G1 (PMID:10891491, PMID:12048210). This function is evolutionarily conserved, as the yeast homolog Erb1p is essential for processing 27SB pre-rRNA to 25S and 5.8S rRNAs (PMID:11522832). Within PeBoW, BOP1 directly binds Pes1 to license Pes1 incorporation into pre-ribosomal complexes, and BOP1 is the central subunit whose loss abolishes copurification of Pes1 with WDR12; BOP1 itself depends on Pes1 for nucleolar import (PMID:15225545, PMID:17353269). Disruption of BOP1-dependent ribosome biogenesis triggers a nucleolar stress response in which RPL11 is released from the nucleolus to the nucleoplasm, inhibiting MDM2, stabilizing p53, and imposing p53-dependent G1 arrest; this stress pathway is genetically separable from the rRNA processing defect itself (PMID:11390653, PMID:33510838). Downstream of stabilized p53, BOP1 loss inhibits mTOR phosphorylation to activate autophagy (PMID:38409361). In cancer contexts, BOP1 overexpression promotes chromosomal instability through activation of Aurora kinase B (PMID:32805281), drives epithelial-to-mesenchymal transition and invasion via RhoA activation (PMID:21520196), and enhances Wnt/β-catenin signaling by recruiting CBP to β-catenin to increase its acetylation and stemness gene transcription (PMID:33797754).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Established BOP1 as a nucleolar factor physically and functionally tied to large-subunit rRNA maturation, answering what cellular process it serves.

    Evidence Sucrose gradient fractionation, pulse-chase rRNA processing, and dominant-negative Bop1Delta in mammalian cells

    PMID:10891491

    Open questions at the time
    • Does not identify partner proteins in the pre-ribosomal particle
    • Catalytic versus scaffold role left undefined
  2. 2001 High

    Showed that the cell cycle arrest caused by BOP1 perturbation is mediated by a p53-dependent nucleolar stress pathway and is uncoupled from the rRNA processing defect itself.

    Evidence Dominant-negative expression with p53 inactivation epistasis, CDK/pRb and p21/p27 readouts

    PMID:11390653

    Open questions at the time
    • Molecular sensor linking biogenesis defect to p53 not yet identified
    • Does not define which ribosomal protein relays the signal
  3. 2001 High

    Demonstrated evolutionary conservation by showing the yeast ortholog Erb1p is essential for 27SB pre-rRNA processing, generalizing the large-subunit maturation role.

    Evidence Gene disruption and conditional depletion with rRNA processing analysis in S. cerevisiae

    PMID:11522832

    Open questions at the time
    • Conservation of the human p53 stress link not addressable in yeast
  4. 2002 High

    Mapped the precise processing sites requiring BOP1 and confirmed the requirement with endogenous knockdown, sharpening its biochemical role.

    Evidence Deletion mutagenesis, antisense knockdown, immunofluorescence and rRNA processing analysis

    PMID:12048210

    Open questions at the time
    • Whether BOP1 acts catalytically or recruits processing nucleases unresolved
  5. 2004 High

    Defined a direct BOP1–Pes1 interaction required for Pes1 entry into pre-ribosomal complexes, identifying the first physical partner.

    Evidence Co-immunoprecipitation and dominant-negative Pes1 mutant panel with rRNA and cell cycle assays

    PMID:15225545

    Open questions at the time
    • Interaction interface not structurally resolved
    • Stoichiometry not defined
  6. 2005 High

    Identified the trimeric PeBoW complex (BOP1–Pes1–WDR12) and showed WDR12 is also required for 32S processing and proliferation.

    Evidence Co-immunoprecipitation, dominant-negative WDR12, rRNA processing and p53 accumulation assays

    PMID:16043514

    Open questions at the time
    • Order of assembly not yet established
    • p19ARF-independent route to p53 not mechanistically detailed
  7. 2007 High

    Established BOP1 as the central, complex-organizing subunit and defined Pes1-dependent nucleolar import, clarifying assembly architecture and trafficking.

    Evidence Recombinant reconstitution, co-IP, siRNA, fractionation and sucrose gradient centrifugation

    PMID:17353269

    Open questions at the time
    • No high-resolution structure of the assembled complex
    • Mechanism of Pes1-dependent transport unknown
  8. 2006 Low

    First hint of a mitotic role: BOP1 overexpression increased multipolar spindles, suggesting function beyond ribosome biogenesis.

    Evidence BOP1 overexpression with immunofluorescence of spindle morphology

    PMID:16804918

    Open questions at the time
    • Single overexpression experiment, single method
    • Molecular link to spindle defects not defined
  9. 2011 Medium

    Connected BOP1 overexpression to EMT and motility via RhoA activation in hepatocellular carcinoma, extending its biology to a pro-metastatic axis.

    Evidence siRNA and ectopic expression with invasion/migration assays, EMT markers and RhoA activation assay

    PMID:21520196

    Open questions at the time
    • Mechanism linking BOP1 to RhoA not defined
    • Single-lab cancer-cell context
  10. 2019 Medium

    Identified BOP1 loss as a driver of BRAF-inhibitor resistance through transcriptional downregulation of DUSP4/DUSP6 and elevated MAPK signaling.

    Evidence shRNA epigenetic-regulator screen, knockdown, DUSP expression and MAPK assays, mouse studies

    PMID:30782837

    Open questions at the time
    • Direct mechanism by which BOP1 controls DUSP transcription unknown
    • Relationship to ribosome biogenesis role unclear
  11. 2020 Medium

    Linked CCAT2-driven BOP1 overexpression to chromosomal instability via Aurora kinase B activation, providing a mechanism for the earlier spindle phenotype.

    Evidence MS2/RIP/SHAPE RNA-protein analysis, overexpression/knockdown, cytogenetics and immunofluorescence

    PMID:32805281

    Open questions at the time
    • How BOP1 activates AURKB mechanistically not resolved
    • Single lab
  12. 2021 Medium

    Demonstrated that BOP1 overexpression amplifies Wnt/β-catenin signaling by recruiting CBP to β-catenin to enhance acetylation and stemness, defining a transcriptional oncogenic axis.

    Evidence Overexpression/knockdown, BOP1-CBP-β-catenin co-IP, acetylation assay, drug-resistance assays in vitro and in vivo

    PMID:33797754

    Open questions at the time
    • Whether BOP1 directly contacts β-catenin or CBP not fully resolved
    • Single lab
  13. 2021 Medium

    Mapped the nucleolar stress effector chain in vascular smooth muscle: BOP1 loss → RPL11 release → MDM2 inhibition → p53 stabilization → suppressed proliferation.

    Evidence BOP1/RPL11 siRNA, pifithrin-α p53 inhibition, proliferation/migration assays and rat balloon injury model

    PMID:33510838

    Open questions at the time
    • Generality across cell types not established by this study alone
    • Single lab
  14. 2024 Medium

    Extended the RPL11–MDM2–p53 axis downstream to mTOR inhibition and autophagy activation, with in vivo rescue of PCOS phenotypes.

    Evidence Lentiviral knockdown/overexpression, pathway analysis and in vivo PCOS mouse model

    PMID:38409361

    Open questions at the time
    • Direct versus indirect coupling of p53 to mTOR not dissected
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BOP1's non-canonical signaling activities (AURKB, RhoA, CBP/β-catenin, DUSP/MAPK) mechanistically arise from or are independent of its core ribosome-biogenesis scaffold function remains unresolved.
  • No structural model of PeBoW
  • No demonstrated direct enzymatic substrate for BOP1
  • Whether signaling roles require nucleolar localization is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005730 nucleolus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
CREBBPCTNNB1PES1RPL11WDR12
Complex memberships
PeBoW complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Bop1 is a WD40 repeat nucleolar protein that cosediments with 50S-80S ribonucleoprotein particles containing 32S rRNA precursor; expression of dominant-negative Bop1Delta (lacking 231 N-terminal amino acids) specifically blocks conversion of 36S to 32S pre-rRNA and completely inhibits processing of 32S pre-rRNA to mature 28S and 5.8S rRNAs, causing deficiency of cytosolic 60S ribosomal subunits and G1 cell cycle arrest. Immunofluorescence, sucrose density gradient fractionation, pulse-chase rRNA processing analysis, dominant-negative expression Molecular and cellular biology High 10891491
2001 Perturbation of Bop1 by dominant-negative Bop1Delta induces p53-dependent G1 cell cycle arrest; inactivation of p53 abrogates this arrest without restoring normal rRNA processing, demonstrating that deficiencies in ribosome synthesis trigger cell cycle arrest via a p53-dependent nucleolar stress pathway, and that rRNA processing defects can be uncoupled from cell cycle arrest. Dominant-negative expression, p53 inactivation, CDK kinase activity assays, pRb phosphorylation analysis, p21/p27 western blotting Molecular and cellular biology High 11390653
2001 The yeast homolog of Bop1, Erb1p (encoded by YMR049C), is essential for viability and required for processing of 27SB pre-rRNA to 25S and 5.8S rRNAs; Erb1p depletion causes loss of 25S and 5.8S rRNAs with underaccumulation of 27SB pre-rRNA, demonstrating evolutionary conservation of Bop1/Erb1p function in large ribosomal subunit maturation. Gene disruption, conditional depletion, rRNA processing analysis in S. cerevisiae Nucleic acids research High 11522832
2002 Bop1 is required for pre-rRNA processing at four distinct sites within ITS1, ITS2, and the 3' external spacer; both C-terminal (Bop1N2) and N-terminal (Bop1Delta) deletion mutants localize to the nucleolus and inhibit rRNA processing and cell cycle progression, and antisense oligonucleotide knockdown of endogenous Bop1 recapitulates processing defects. Deletion mutagenesis, antisense oligonucleotide knockdown, immunofluorescence, rRNA processing analysis The Journal of biological chemistry High 12048210
2004 Bop1 physically interacts with Pes1 (mouse homolog of yeast Nop7p); this interaction is essential for efficient incorporation of Pes1 into nucleolar preribosomal complexes, and Pes1 mutants defective for Bop1 interaction lose the ability to affect rRNA maturation and the cell cycle. Co-immunoprecipitation, dominant-negative Pes1 mutant panel, rRNA processing analysis, cell cycle assays Molecular cell High 15225545
2005 Bop1 and Pes1 form a stable trimeric complex with WDR12 (a novel WD40 repeat protein), termed the PeBoW complex; endogenous WDR12 is required for processing of 32S precursor rRNA and cell proliferation, and a dominant-negative WDR12 mutant blocks rRNA processing and induces p53 accumulation in a p19ARF-independent manner. Co-immunoprecipitation, dominant-negative expression, rRNA processing assays, p53 accumulation analysis The Journal of cell biology High 16043514
2007 Bop1 is the integral/central component of the PeBoW complex: recombinant expression of Pes1, Bop1, and WDR12 is sufficient for complex formation; Bop1 knockdown abolishes copurification of Pes1 with WDR12; overexpressed Bop1 inhibits cell proliferation and rRNA processing (rescuable by WDR12 co-expression but not Pes1); nucleolar transport of Bop1 from cytoplasm is Pes1-dependent, while Pes1 migrates to nucleolus independently of Bop1. Recombinant protein expression, co-immunoprecipitation, siRNA knockdown, immunofluorescence, cell fractionation, sucrose gradient centrifugation Molecular and cellular biology High 17353269
2020 BOP1 promotes chromosomal instability by increasing the active form of Aurora kinase B (AURKB), which regulates chromosomal segregation; CCAT2 lncRNA directly binds and stabilizes BOP1 protein and also activates MYC-driven BOP1 transcription, leading to BOP1 overexpression that causes chromosomal missegregation errors. MS2 pull-down, RNA immunoprecipitation, SHAPE analysis, BOP1 overexpression/knockdown, cytogenetic analysis, immunofluorescence Gastroenterology Medium 32805281
2019 Loss of BOP1 confers resistance to BRAF kinase inhibitors in melanoma by downregulating MAPK phosphatases DUSP4 and DUSP6 via a transcription-based mechanism, leading to increased MAPK signaling. shRNA screen (363 epigenetic regulators), BOP1 knockdown, DUSP4/DUSP6 expression analysis, MAPK pathway activity assays, in vivo mouse studies Proceedings of the National Academy of Sciences of the United States of America Medium 30782837
2011 BOP1 promotes epithelial-to-mesenchymal transition (EMT) in hepatocellular carcinoma cells, stimulates actin stress fiber assembly, and activates RhoA; siRNA-mediated BOP1 knockdown upregulates epithelial markers (E-cadherin, cytokeratin 18, γ-catenin) and downregulates mesenchymal markers (fibronectin, vimentin), while ectopic BOP1 expression in hepatocytes increases invasiveness and migration. siRNA knockdown, ectopic overexpression, invasion/migration assays, EMT marker western blotting, RhoA activation assay, actin staining Hepatology (Baltimore, Md.) Medium 21520196
2021 BOP1 activates Wnt/β-catenin signaling in triple-negative breast cancer by increasing recruitment of CBP (CREB-binding protein) to β-catenin, enhancing CBP-mediated acetylation of β-catenin, and increasing transcription of stemness-related genes CD133 and ALDH1A1, thereby promoting cancer stem cell-like phenotype and chemoresistance. BOP1 overexpression/knockdown, Co-immunoprecipitation (BOP1-CBP-β-catenin), acetylation assay, gene expression analysis, in vitro and in vivo drug resistance assays The Journal of pathology Medium 33797754
2021 BOP1 knockdown in vascular smooth muscle cells activates nucleolar stress, causing RPL11 release from nucleolus to nucleoplasm, which inhibits MDM2 E3 ubiquitin ligase activity, stabilizes p53, and subsequently inhibits VSMC proliferation and migration; siRNA knockdown of RPL11 or p53 inhibition with pifithrin-α partially reverses these effects. siRNA knockdown of BOP1 and RPL11, p53 inhibitor (pifithrin-α), proliferation/migration assays, nascent protein synthesis assay, rat balloon injury model Oxidative medicine and cellular longevity Medium 33510838
2024 BOP1 knockdown triggers nucleolar stress response causing RPL11 release from nucleolus into nucleoplasm, inhibiting MDM2, stabilizing p53, which then inhibits mTOR phosphorylation, activating autophagy in granulosa cells; BOP1 overexpression in vivo suppresses this pathway and alleviates PCOS phenotypes. BOP1 knockdown/overexpression (lentiviral), RPL11 localization, MDM2 inhibition, p53/mTOR pathway analysis, in vivo PCOS mouse model Cellular and molecular life sciences : CMLS Medium 38409361
2006 Transient overexpression of BOP1 in human cells increases the percentage of multipolar spindles, indicating a role for BOP1 in proper chromosome segregation beyond its function in ribosome biogenesis. BOP1 overexpression, immunofluorescence analysis of spindle morphology Genes, chromosomes & cancer Low 16804918
2023 BOP1 promotes prostate cancer cell viability and metastasis via regulation of DUSP6 expression and activation of the MAPK pathway; BOP1 knockout inhibits DUSP6 expression and MAPK signaling, and DUSP6 overexpression reverses the effects of BOP1 siRNA. BOP1 knockout/siRNA, DUSP6 overexpression, MAPK pathway western blotting, Transwell invasion assay, apoptosis assay Archivos espanoles de urologia Low 37681336
2022 lncRNA SNHG6 binds BOP1 protein and enhances its stability, promoting glycolysis and proliferation in hepatocellular carcinoma cells; BOP1 overexpression rescues proliferation and glycolysis changes caused by SNHG6 manipulation. MS2 pull-down, RNA pull-down, RNA immunoprecipitation (RIP), western blotting, glucose uptake/lactate/OCR/ECAR assays Animal cells and systems Low 36605586
2025 BOP1 depletion reduces overall ribosome availability, which preferentially upregulates translation of non-optimal codon transcripts (including several ISGs) during IFN-β stimulation, demonstrating that ribosome biogenesis controlled by BOP1 regulates translational fine-tuning through codon optimality. RNA-seq, LC-MS/MS proteomics (multi-omics), BOP1 knockdown, codon usage analysis, reporter constructs (codon-optimal vs non-optimal) bioRxivpreprint Low bio_10.1101_2025.09.05.673799

Source papers

Stage 0 corpus · 25 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: effects of nucleolar protein Bop1 on G(1)/S transition. Molecular and cellular biology 297 11390653
2005 Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation. The Journal of cell biology 165 16043514
2000 Bop1 is a mouse WD40 repeat nucleolar protein involved in 28S and 5. 8S RRNA processing and 60S ribosome biogenesis. Molecular and cellular biology 156 10891491
2020 The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling. Gastroenterology 113 32805281
2004 Physical and functional interaction between Pes1 and Bop1 in mammalian ribosome biogenesis. Molecular cell 113 15225545
2007 Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit. Molecular and cellular biology 112 17353269
2002 Functional inactivation of the mouse nucleolar protein Bop1 inhibits multiple steps in pre-rRNA processing and blocks cell cycle progression. The Journal of biological chemistry 91 12048210
2001 ERB1, the yeast homolog of mammalian Bop1, is an essential gene required for maturation of the 25S and 5.8S ribosomal RNAs. Nucleic acids research 65 11522832
2011 Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition. Hepatology (Baltimore, Md.) 64 21520196
2006 Contribution of the BOP1 gene, located on 8q24, to colorectal tumorigenesis. Genes, chromosomes & cancer 55 16804918
2016 A Homolog of Blade-On-Petiole 1 and 2 (BOP1/2) Controls Internode Length and Homeotic Changes of the Barley Inflorescence. Plant physiology 41 27208226
2019 Loss of BOP1 confers resistance to BRAF kinase inhibitors in melanoma by activating MAP kinase pathway. Proceedings of the National Academy of Sciences of the United States of America 34 30782837
2021 BOP1 confers chemoresistance of triple-negative breast cancer by promoting CBP-mediated β-catenin acetylation. The Journal of pathology 23 33797754
2024 BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response. Cellular and molecular life sciences : CMLS 12 38409361
2022 LncRNA SNHG6 promotes glycolysis reprogramming in hepatocellular carcinoma by stabilizing the BOP1 protein. Animal cells and systems 12 36605586
2021 BOP1 Knockdown Attenuates Neointimal Hyperplasia by Activating p53 and Inhibiting Nascent Protein Synthesis. Oxidative medicine and cellular longevity 10 33510838
2020 Expression, Localization, and Function of the Nucleolar Protein BOP1 in Prostate Cancer Progression. The American journal of pathology 9 33039351
2009 Estrogen down-regulation of the Scx gene is mediated by the opposing strand-overlapping gene Bop1. The Journal of biological chemistry 7 19996321
2008 Interaction of BOP1, a protein for ribosome biogenesis, with EB1 in Giardia lamblia. Parasitology research 7 18670790
2005 Interaction of beta-giardin with the Bop1 protein in Giardia lamblia. Parasitology research 7 16362343
2021 BOP1 Silencing Suppresses Gastric Cancer Proliferation through p53 Modulation. Current medical science 6 33877544
2024 Cotton BOP1 mediates SUMOylation of GhBES1 to regulate fibre development and plant architecture. Plant biotechnology journal 4 39003587
2023 PDGF-C promotes cell proliferation partially via downregulating BOP1. Cell biology international 2 37615370
2023 BOP1 Promotes Prostate Cancer through the DUSP6/MAPK Pathway. Archivos espanoles de urologia 2 37681336
2023 Bop1 is required to establish precursor domains of craniofacial tissues. Genesis (New York, N.Y. : 2000) 2 37974491

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