Affinage

RB1

Retinoblastoma-associated protein · UniProt P06400

Length
928 aa
Mass
106.2 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RB1 (pRB) is a tumor suppressor that restrains cell cycle progression by binding E2F transcription factors and converting their target promoters into transcriptionally silent chromatin (PMID:11484059, PMID:9326598). pRB does not act simply as a steric blockade: it recruits the H3K9 methyltransferase SUV39H1 and the methyl-lysine reader HP1 to genes such as cyclin E and cyclin A2, directing histone H3 Lys9 methylation and chromatin-level repression (PMID:11484059), and it physically engages the SWI/SNF ATPase hBRM to repress E2F1 activity through its RB-binding and NTP-binding modules (PMID:9326598). Through a cell-cycle-independent interaction with E2F1, pRB also delivers EZH2 to repetitive genomic sequences (satellites, LINEs, endogenous retroviruses), maintaining H3K27me3 and silencing these loci—an activity abolished by the F832A pocket mutation (PMID:27889452). pRB activity is set by its phosphorylation state: sequential CDK2/CDK4-6 phosphorylation begins at T373 to create a chromatin-bound, reversibly uncommitted intermediate before hyperphosphorylation fully releases E2F and commits cells to S phase (PMID:38926571), while active hypophosphorylated pRB enforces the late G1/S boundary largely by repressing and destabilizing cyclin A (PMID:12027450). These phosphorylation events are tuned by additional modifications—SMYD2 methylation at K810 primes pRB for CDK phosphorylation (PMID:22787429)—and reversed by PP1-based phosphatase activities, including a NORE1A/PP1A complex that activates pRB during Ras-induced senescence (PMID:26677227). Beyond E2F control, pRB acts as a stabilizing cofactor for lineage transcription factors, binding and protecting Pdx-1 in pancreatic β-cells (PMID:21399612), potentiating Runx2-driven osteogenesis while suppressing adipogenesis to govern mesenchymal fate (PMID:20686481), and cooperating with Mitf to induce p21Cip1-dependent G1 arrest (PMID:15716956); a separation-of-function knock-in (R654W) demonstrates that some differentiation roles are genetically independent of E2F1/2/3 binding (PMID:16449662). pRB additionally functions in autophagy (PMID:20807803), satellite-cell quiescence (PMID:21478154), suppression of EMT and metastasis through ZEB1 and the RHAMM/ROCK axis (PMID:27645778, PMID:27923835), and apoptosis, where caspase-3 cleaves its C-terminus and the uncleavable form acts as a death inhibitor (PMID:9695821). RB1 transcription is itself feedback-regulated by E2F and RB-family proteins binding its promoter (PMID:20100864) and activated by an RB1CC1/FIP200-containing nuclear complex (PMID:19437535, PMID:20614030).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Established that pRB represses E2F not merely by binding it but by physically recruiting a chromatin-remodeling ATPase, introducing the concept of pRB as a co-repressor scaffold.

    Evidence Co-IP and structure-function mutagenesis showing pRB simultaneously binds E2F1 and hBRM and cooperatively represses E2F1 transcription

    PMID:9326598

    Open questions at the time
    • Did not resolve whether hBRM acts on nucleosome positioning at endogenous E2F promoters
    • No genome-wide map of pRB-hBRM co-occupancy
  2. 1998 Medium

    Defined pRB as a node in apoptotic signaling by showing caspase cleavage inactivates it, linking its degradation to death-signal execution.

    Evidence In vitro caspase cleavage assays, RB phospho-form immunoblotting, and a caspase-resistant mutant in TNF-α death assays

    PMID:9695821

    Open questions at the time
    • Physiological caspase responsible in vivo not fully defined
    • Downstream consequences of the cleaved fragment unresolved
  3. 1999 Medium

    Placed pRB and p27 on overlapping but non-linear tumor-suppressor pathways, showing combinatorial control of endocrine tumorigenesis.

    Evidence Rb+/- x p27-/- double-mutant mouse genetics with tumor phenotype and p27 expression analysis

    PMID:10339596

    Open questions at the time
    • Molecular basis of cooperativity not delineated
    • Tissue specificity of the genetic interaction unexplained
  4. 2001 High

    Revealed the chromatin-silencing mechanism of pRB repression—recruitment of SUV39H1/HP1 to deposit H3K9 methylation at cell-cycle promoters—and its link to Polycomb-mediated mitotic control.

    Evidence Reciprocal Co-IP, ChIP on the cyclin E promoter in SUV39H1-knockout fibroblasts; separate Co-IP/colocalization with PcG complexes and cell-cycle readouts

    PMID:11484059 PMID:11583618

    Open questions at the time
    • Generality of HP1/SUV39H1 recruitment across the E2F target set not established
    • PcG-pRB complex composition only partially defined (Medium-confidence)
  5. 2002 Medium

    Clarified how active pRB enforces the late G1/S boundary, showing the block operates through cyclin A repression and degradation rather than cyclin E/CDK2 suppression.

    Evidence Inducible constitutively active PSM-RB allele with CDK kinase assays, mRNA/protein and centrosome duplication readouts

    PMID:12027450

    Open questions at the time
    • Mechanism of accelerated cyclin A degradation not identified
    • Single inducible system
  6. 2006 High

    Expanded pRB's repressive repertoire and differentiation roles—identifying PRMT2 as an RB-dependent E2F1 co-repressor, Runx2/PPARγ control of mesenchymal fate, and an E2F-independent differentiation function via the R654W separation-of-function allele.

    Evidence PRMT2-null MEFs and ternary-complex Co-IP; conditional Rb knockout lineage tracing; R654W knock-in mouse rescue of erythroid/macrophage but not retinal defects

    PMID:16449662 PMID:16616919 PMID:20686481

    Open questions at the time
    • Identity of the E2F-independent effectors in differentiation tissues unknown
    • Whether PRMT2 methylation activity is required for repression not resolved
  7. 2009 Medium

    Showed RB1 expression is transcriptionally controlled by FIP200/RB1CC1 binding its promoter, identifying an upstream regulator of pRB abundance.

    Evidence ChIP, EMSA, and luciferase reporter assays mapping RB1CC1 binding to a GC-rich element upstream of RB1

    PMID:19437535

    Open questions at the time
    • Physiological signals controlling RB1CC1 nuclear activity unclear
    • Single-lab promoter study
  8. 2010 Medium

    Extended pRB function into autophagy, neuronal migration, and protein-stabilizing cofactor roles, and defined an RB1CC1/hSNF5/p53 transcriptional activation complex for RB1, p16 and p21.

    Evidence RB/E2F1 epistasis autophagy assays; ChIP/reporter and conditional KO for neogenin; Co-IP/RIM mutagenesis stabilizing Pdx-1; Co-IP/ChIP for the RB1CC1-hSNF5-p53 complex

    PMID:20614030 PMID:20807803 PMID:21059867 PMID:21399612

    Open questions at the time
    • Autophagy effector genes downstream of E2F1 unidentified
    • Whether the RB1CC1-p53 complex operates in normal vs stressed cells unclear
  9. 2011 Medium

    Defined pRB as a guardian of stem-cell quiescence, showing its loss drives quiescent satellite cells back into cycle while impairing differentiation.

    Evidence Pax7CreER;Rb1flox conditional knockout with cell counting, BrdU, injury/regeneration, and PP1 inhibition

    PMID:21478154

    Open questions at the time
    • Phosphatase regulating pRB in satellite cells not definitively identified
    • Single in vivo system
  10. 2012 High

    Identified a post-translational priming mechanism—SMYD2 methylation of pRB at K810 enhancing CDK phosphorylation—linking lysine methylation to cell-cycle release.

    Evidence In vitro methyltransferase assay with LC-MS/MS site mapping, Co-IP, and SMYD2-knockdown cell-cycle analysis

    PMID:22787429

    Open questions at the time
    • Reader of K810 methylation not identified
    • Whether methylation directly alters CDK docking unresolved
  11. 2015 Medium

    Connected pRB activation to oncogene-induced senescence through a Ras/NORE1A/PP1A dephosphorylation circuit.

    Evidence Co-IP of NORE1A-PP1A, RB suppression epistasis, and senescence assays

    PMID:26677227

    Open questions at the time
    • Direct PP1A dephosphorylation sites on pRB not mapped
    • Single-lab study
  12. 2016 High

    Defined a cell-cycle-independent pRB-EZH2 repeat-silencing activity and additional non-cell-cycle modifications and effectors (sumoylation/Lamin A/C protection, ZEB1/RHAMM-mediated suppression of EMT and metastasis).

    Evidence F832A knock-in mouse with ChIP-seq for EZH2/H3K27me3; SUMO/SENP1 assays for Lamin A/C; PNUTS knockdown 3D culture for ZEB1; multiple RB-knockout cancer models for RHAMM/ROCK

    PMID:27270425 PMID:27645778 PMID:27889452 PMID:27923835

    Open questions at the time
    • How a single pocket residue (F832) discriminates repeat from gene targets unclear
    • Sumoylation and ZEB1 findings are Medium-confidence single-lab studies
  13. 2018 Medium

    Identified ASPH as a scaffolding factor promoting RB1-CDK-cyclin complex assembly and pRB phosphorylation in cancer.

    Evidence Co-IP, ASPH knockdown with phospho-RB1 readout, xenograft model, and dioxygenase inhibition

    PMID:29733964

    Open questions at the time
    • Whether ASPH hydroxylase activity is required for complex assembly not resolved
    • Single-lab study
  14. 2024 High

    Resolved how pRB inactivation is graded over the cell cycle, showing T373 phosphorylation creates a chromatin-bound, reversibly uncommitted intermediate that precedes full hyperphosphorylation and S-phase commitment.

    Evidence Single-cell live imaging of E2F/CDK2 reporters, phospho-site-specific immunofluorescence, and pharmacological CDK inhibition

    PMID:38926571

    Open questions at the time
    • Structural basis of partial vs full E2F release not defined
    • Phosphatase setting the slow T373 dephosphorylation rate not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many pRB modifications (phosphorylation, K810 methylation, sumoylation, caspase cleavage) and its diverse partner set are integrated to select among proliferation, differentiation, senescence, autophagy, and apoptosis outcomes in a given cell remains unresolved.
  • No unified model linking modification state to effector-complex choice
  • Tissue-specific partner usage incompletely mapped
  • Structural basis for pocket-domain discrimination among E2F, lineage factors, and co-repressors undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 2 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 2 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-8953897 Cellular responses to stimuli 1 R-HSA-9612973 Autophagy 1
Partners
E2F1EZH2HBRMHP1MITFPDX-1PRMT2SUV39H1
Complex memberships
pRB-E2F1-EZH2 repeat-silencing complexpRB-E2F1-hBRM (SWI/SNF) repressor complexpRB-PcG repressor complexpRB-SUV39H1-HP1 repressor complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 RB associates with the histone methyltransferase SUV39H1 and the methyl-lysine binding protein HP1 via its pocket domain in vivo. RB directs methylation of histone H3 (Lys9) and recruits HP1 to the cyclin E promoter, repressing cyclin E and cyclin A2 gene expression through chromatin-level silencing. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), transient transfection reporter assays, SUV39H1-disrupted fibroblasts Nature High 11484059
1997 RB physically interacts with hBRM (a SWI/SNF ATPase subunit) and can simultaneously bind both E2F1 and hBRM, targeting hBRM to E2F1. RB and hBRM cooperate to repress E2F1 transcriptional activity, and this cooperation requires the RB-binding domain and NTP-binding site of hBRM but not its bromodomain. Co-immunoprecipitation in vivo, transient transfection reporter assays, domain-deletion and mutation analysis Proceedings of the National Academy of Sciences of the United States of America High 9326598
2012 SMYD2 methylates RB1 protein at lysine 810 in vitro and in vivo. This lysine 810 methylation enhances subsequent phosphorylation of RB1 at Ser807/811, accelerates E2F transcriptional activity, and promotes cell cycle progression through G1/S. In vitro methyltransferase assay, LC-MS/MS identification of methylation site, immunoprecipitation, cell cycle analysis, SMYD2 knockdown Neoplasia (New York, N.Y.) High 22787429
2001 RB colocalizes with Polycomb group (PcG) protein complexes in the nucleus and forms a repressor complex with PcG proteins that blocks entry into mitosis. RB is required for the association of PcG complexes with their nuclear targets. Co-immunoprecipitation, immunofluorescence colocalization, cell cycle analysis Molecular cell Medium 11583618
2016 pRB uses a cell-cycle-independent interaction with E2F1 to recruit EZH2 to diverse repetitive genomic sequences (simple repeats, satellites, LINEs, endogenous retroviruses). An F832A point mutation in Rb1 abolishes this recruitment; loss of pRB-EZH2 complexes disperses H3K27me3 from these repeat loci and permits their expression. Co-immunoprecipitation, ChIP-seq, knock-in mouse model (F832A mutation), gene expression analysis Molecular cell High 27889452
2024 CDK2- or CDK4/6-mediated phosphorylation of RB1 at the conserved T373 residue creates a primed, intermediate state of partial E2F activation. T373-phosphorylated RB remains bound to chromatin but dissociates fully only upon hyperphosphorylation at many sites. T373 is preferentially phosphorylated initially due to its slower dephosphorylation rate. This intermediate state allows cells to remain reversibly uncommitted before triggering the positive CDK2-E2F feedback loop. Single-cell live imaging of E2F and CDK2 reporters, phospho-specific immunofluorescence, pharmacological CDK inhibition, site-specific RB phosphorylation analysis Nature High 38926571
2006 The arginine methyltransferase PRMT2 binds RB through its AdoMet binding domain (unlike PRMT1, PRMT3, PRMT4 which do not bind RB). PRMT2 represses E2F1 transcriptional activity in an RB-dependent manner by forming a ternary complex with E2F1 in the presence of RB. PRMT2-null MEFs show increased E2F activity and accelerated S-phase entry. Co-immunoprecipitation, reporter assays, PRMT2 gene targeting in mice, cell cycle analysis Experimental cell research High 16616919
2010 RB physically associates with and stabilizes the pancreatic transcription factor Pdx-1 via a conserved RB-interaction motif (RIM) in Pdx-1 that is also present in E2Fs. Point mutations within the RIM reduce RB-Pdx-1 complex formation, destabilize Pdx-1, and promote its proteasomal degradation. Glucose regulates RB/Pdx-1 complex formation and Pdx-1 stability. RB occupies promoters of β-cell-specific genes; RB knockdown reduces Pdx-1 and its target gene expression. Co-immunoprecipitation, site-directed mutagenesis (RIM mutations), ChIP, siRNA knockdown, proteasome inhibitor experiments, RB-deficient mouse phenotype The EMBO journal High 21399612
2016 Dephosphorylated RB associates with ZEB1 (a transcriptional regulator of EMT markers E- and N-cadherin) and inhibits ZEB1 transcriptional activity. PP1-mediated dephosphorylation of RB (via PNUTS knockdown) reduces EMT in invasive cancer cells in 3D culture in an RB-dependent manner. shRNA silencing of PNUTS, Co-immunoprecipitation, 3D Matrigel culture, reporter assays, Western blot Cancer biology & therapy Medium 27645778
2016 SUMO1 conjugation of RB and Lamin A/C, modulated by the SUMO protease SENP1, is required for the RB-Lamin A/C interaction. This SUMO1-dependent complex protects both RB and Lamin A/C from proteasomal degradation. Sumoylation assays, Co-immunoprecipitation, SENP1 overexpression/knockdown, proteasome inhibitor experiments Oncogene Medium 27270425
2010 RB triggers autophagy through repression of E2F1 activity. RB activators p16INK4a and p27/Kip1 induce autophagy in an RB-dependent manner. E2F1 antagonizes RB-induced autophagy, and downregulation of E2F1 leads to high autophagy levels. Autophagy assays, RB/E2F1 overexpression and knockdown, epistasis by double knockdown Cancer research Medium 20807803
2015 Ras induces formation of a complex between NORE1A and the phosphatase PP1A, which promotes dephosphorylation and activation of RB. Suppression of RB reduces NORE1A-induced senescence, placing RB downstream of Ras/NORE1A/PP1A in oncogene-induced senescence. Co-immunoprecipitation, RB knockdown, senescence assays, PP1A-NORE1A interaction pulldown The Journal of biological chemistry Medium 26677227
2018 Aspartate beta-hydroxylase (ASPH) promotes direct protein interaction between RB1, cyclin-dependent kinases, and cyclins, thereby promoting RB1 phosphorylation. ASPH knockdown reduces RB1 phosphorylation and inhibits cholangiocarcinoma growth in vitro and in vivo. Co-immunoprecipitation, ASPH knockdown, phospho-RB1 immunoassay, xenograft mouse model, 2-OG dioxygenase inhibitor treatment Cancer letters Medium 29733964
2002 Active (constitutively hypophosphorylated) RB inhibits cell cycle progression at the late G1/S boundary not by suppressing cyclin E expression or CDK2/cyclin E activity, but by causing coordinate transcriptional repression and accelerated degradation of cyclin A, attenuating CDK2/cyclin A-dependent events. Inducible constitutively active RB allele (PSM-RB), cell cycle synchronization, mRNA and protein analysis, CDK kinase assays, centrosome duplication assay Experimental cell research Medium 12027450
2006 Rb1 protein (pRb) binds to Runx2 and potentiates its osteogenic differentiation activity. pRb acts with E2F to suppress PPARγ (master adipogenic activator). Rb status thus controls mesenchymal stem cell fate choice between osteoblast and adipocyte lineages in vivo. Mouse conditional knockout models, lineage tracing, in vivo bone and adipose tissue phenotyping, co-immunoprecipitation (referenced in abstract as prior in vitro work; in vivo epistasis confirmed here) Nature Medium 20686481
1998 RB1 is cleaved by caspase-3-like activity at its carboxyl terminus during apoptosis. During apoptosis, hyperphosphorylated RB is first dephosphorylated to the hypophosphorylated form, which is then cleaved by caspase activity. The unphosphorylated (p110) form of RB is resistant to cleavage and functions as an inhibitor of apoptosis; a caspase-resistant RB1 attenuates the death response to TNF-α. In vitro caspase cleavage assays, cell death assays with TNF-α, immunoblotting of RB phospho-forms, caspase-resistant mutant expression Trends in cell biology Medium 9695821
2009 RB1CC1 (FIP200) directly binds to a GC-rich region 201 bp upstream of the RB1 promoter and activates RB1 transcription. The C-terminus of RB1CC1 is required for its nuclear localization and subsequent RB1 promoter activation. Chromatin immunoprecipitation, luciferase reporter assays, electrophoretic mobility shift assay (EMSA), Western blot, immunohistochemistry International journal of cancer Medium 19437535
2010 RB1CC1 (FIP200) forms a nuclear complex with hSNF5 and/or p53 that activates transcription of RB1, p16, and p21. RB1CC1 binds hSNF5 and p53 as identified by immunoprecipitation and immunofluorescence. Co-immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assays, flow cytometry, immunofluorescence PloS one Medium 20614030
2010 The RB/E2F pathway directly regulates neogenin expression: RB represses E2F-mediated transcription of neogenin (a receptor for netrin-1 involved in cell migration), and E2F3 occupies E2F consensus sites on the neogenin promoter in native chromatin. Loss of Rb results in increased neogenin expression, aberrant neuronal migration and adhesion in response to netrin-1. ChIP, promoter reporter assays, Rb conditional knockout mouse, ex vivo electroporation, migration assays Molecular and cellular biology Medium 21059867
2011 Loss of Rb1 in satellite cells (using conditional Pax7CreER;Rb1 deletion) causes re-entry of quiescent satellite cells into replication, resulting in 5-fold expansion of satellite cells and 3-fold increase in myoblasts, while diminishing terminal differentiation. This establishes pRb as a regulator of muscle satellite cell quiescence. Conditional mouse knockout (Pax7CreER;Rb1flox), satellite cell counting, BrdU incorporation, cardiotoxin injury/regeneration assay, pharmacological PP1 inhibition The Journal of biological chemistry Medium 21478154
2005 Mitf cooperates physically with Rb1 to potentiate Mitf-mediated transcriptional activation. The interaction between Mitf and hypophosphorylated Rb1 enhances Mitf's ability to activate the p21Cip1 promoter, leading to G1 arrest. Mitf-induced cell cycle arrest depends on this p21Cip1 induction. Co-immunoprecipitation, luciferase reporter assays, cell cycle analysis, p21Cip1 promoter activation assays Nature Medium 15716956
2006 RB family members (p107 and p130) and E2F transcription factors bind directly to the RB1 promoter in vivo, modulating RB transcription as a regulatory feedback mechanism in specific cell populations. ChIP on RB1 promoter, transgenic eGFP-BAC reporter mice, genetic analyses with Rb, p107, and p130 mutant alleles Molecular and cellular biology Medium 20100864
2016 RB loss induces upregulation of the cell motility receptor RHAMM via the RB/E2F pathway, which stabilizes F-actin polymerization by controlling ROCK signaling, promoting epithelial-mesenchymal transition, motility, and invasion. Pharmacological or genetic inhibition of RHAMM blocks the metastatic phenotype caused by RB loss. Multiple murine cancer models with RB knockout, gene expression analysis, pharmacological RHAMM inhibition, RHAMM genetic modulation, invasion/motility assays, F-actin polymerization assays Cancer research Medium 27923835
2006 An E2F-binding-deficient Rb1 point mutant (R654W, defective for binding E2F1, E2F2, E2F3) rescues erythrocyte and fetal liver macrophage differentiation defects in Rb1-null embryos, extending survival by at least 2 days beyond null lethality, but does not rescue retinal differentiation defects. This establishes that Rb1's role in certain differentiation events is genetically separable from E2F1/2/3 binding. Knock-in mouse model (R654W mutation), embryonic phenotype analysis, histology, cell cycle analysis, comparison with null embryos Molecular and cellular biology High 16449662
1999 Rb and p27 cooperate to suppress tumor development through overlapping but distinct pathways: Rb+/-p27-/- double mutant mice develop more aggressive and earlier-onset pituitary and thyroid tumors than either single mutant, and pituitary tumor development in Rb+/- mice correlates with reduced p27 expression. This genetic epistasis places p27 and Rb on overlapping but not strictly linear tumor suppressor pathways. Mouse double-mutant genetic analysis (Rb+/- x p27-/-), tumor phenotype comparison, p27 mRNA and protein expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 10339596

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The RB and p53 pathways in cancer. Cancer cell 1279 12204530
2006 RB and cell cycle progression. Oncogene 932 16936740
2001 The Rb/E2F pathway and cancer. Human molecular genetics 742 11257102
2001 Rb targets histone H3 methylation and HP1 to promoters. Nature 720 11484059
2013 Molecular mechanisms underlying RB protein function. Nature reviews. Molecular cell biology 465 23594950
2016 RB1: a prototype tumor suppressor and an enigma. Genes & development 353 27401552
1988 Altered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung. Oncogene 309 2856251
2005 Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression. Nature 308 15716956
2010 Rb regulates fate choice and lineage commitment in vivo. Nature 271 20686481
1997 RB and hbrm cooperate to repress the activation functions of E2F1. Proceedings of the National Academy of Sciences of the United States of America 262 9326598
1997 RB kinases and RB-binding proteins: new points of view. Trends in biochemical sciences 226 9020586
2017 Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions. Journal of ginseng research 190 29719458
2014 Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature 186 25252974
2012 RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation. Neoplasia (New York, N.Y.) 169 22787429
2001 Linking the Rb and polycomb pathways. Molecular cell 160 11583618
2010 Targeting the RB-pathway in cancer therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 158 20145169
1989 Mutations in the RB1 gene and their effects on transcription. Molecular and cellular biology 157 2601691
2013 RB1 in cancer: different mechanisms of RB1 inactivation and alterations of pRb pathway in tumorigenesis. Journal of cellular physiology 153 23359405
2019 Cell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy. Trends in cancer 150 31174843
2011 RB1, development, and cancer. Current topics in developmental biology 145 21295686
2016 An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences. Molecular cell 141 27889452
2001 Promoter hypermethylation of the RB1 gene in glioblastomas. Laboratory investigation; a journal of technical methods and pathology 137 11204276
1999 RB1 gene mutations in retinoblastoma. Human mutation 137 10502774
2010 Antiobesity and antihyperglycemic effects of ginsenoside Rb1 in rats. Diabetes 127 20682695
2007 From G0 to S phase: a view of the roles played by the retinoblastoma (Rb) family members in the Rb-E2F pathway. Journal of cellular biochemistry 127 17979151
1999 p27 and Rb are on overlapping pathways suppressing tumorigenesis in mice. Proceedings of the National Academy of Sciences of the United States of America 127 10339596
2012 RB: mitotic implications of a tumour suppressor. Nature reviews. Cancer 124 22318235
2002 RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer. Oncogene 123 12362273
1998 The caspase-RB connection in cell death. Trends in cell biology 122 9695821
2000 Chromatin remodeling and Rb activity. Current opinion in cell biology 105 11063932
2000 A novel Rb- and p300-binding protein inhibits transactivation by MyoD. Molecular and cellular biology 105 11073990
2010 The RB-E2F1 pathway regulates autophagy. Cancer research 102 20807803
2001 Neurotrophic and neuroprotective actions of ginsenosides Rb(1) and Rg(1). Planta medica 99 11509974
2018 Control of the Restriction Point by Rb and p21. Proceedings of the National Academy of Sciences of the United States of America 97 30111539
2014 RB1 gene inactivation by chromothripsis in human retinoblastoma. Oncotarget 93 24509483
2006 RB, the conductor that orchestrates life, death and differentiation. Oncogene 86 16936739
2017 The Retinoblastoma (RB) Tumor Suppressor: Pushing Back against Genome Instability on Multiple Fronts. International journal of molecular sciences 84 28812991
2001 Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendrogliomas. Journal of neuropathology and experimental neurology 83 11764090
2007 Role of Rb-dependent and Rb-independent functions of papillomavirus E7 oncogene in head and neck cancer. Cancer research 82 18089787
2011 Epidemiology and Rb1 gene of retinoblastoma. International journal of ophthalmology 79 22553621
2016 RB Loss Promotes Prostate Cancer Metastasis. Cancer research 76 27923835
1999 Alterations of Rb pathway (Rb-p16INK4-cyclin D1) in preinvasive bronchial lesions. Clinical cancer research : an official journal of the American Association for Cancer Research 74 10037171
1998 Expression of p16 induces transcriptional downregulation of the RB gene. Oncogene 74 9467937
2006 The arginine methyltransferase PRMT2 binds RB and regulates E2F function. Experimental cell research 72 16616919
1994 p53 and Rb: their cellular roles. Current opinion in cell biology 71 7880533
2001 The Rb/chromatin connection and epigenetic control: opinion. Oncogene 67 11420729
2004 Competitive Na(+) and Rb(+) binding in the minor groove of DNA. Journal of the American Chemical Society 65 15161302
2021 Recent progress (2015-2020) in the investigation of the pharmacological effects and mechanisms of ginsenoside Rb1, a main active ingredient in Panax ginseng Meyer. Journal of ginseng research 62 35058726
1992 Studies of the RB1 gene and the p53 gene in human osteosarcomas. Pediatric hematology and oncology 56 1524989
2009 The rb pathway and cancer therapeutics. Current drug targets 55 19601762
2022 Novel insights into RB1 mutation. Cancer letters 54 35964818
2021 Targeting RB1 Loss in Cancers. Cancers 53 34359636
1993 Retinoblastoma (Rb) gene product expression in lymphomas. Correlation with Ki67 growth fraction. The Journal of pathology 53 8501537
1992 Analysis of retinoblastoma (RB) gene deletion in human prostatic carcinomas. The Prostate 52 1329054
2010 Rb/E2F regulates expression of neogenin during neuronal migration. Molecular and cellular biology 50 21059867
2001 The Rb pathway in neurogenesis. Neuroreport 44 11435948
2024 An intermediate Rb-E2F activity state safeguards proliferation commitment. Nature 43 38926571
2021 Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma. Nature communications 43 34862364
2011 Zebrafish usp39 mutation leads to rb1 mRNA splicing defect and pituitary lineage expansion. PLoS genetics 43 21249182
2007 RB1 and TP53 pathways in radiation-induced sarcomas. Oncogene 42 17369843
2019 The SOX4/miR-17-92/RB1 Axis Promotes Prostate Cancer Progression. Neoplasia (New York, N.Y.) 39 31238254
2015 NUSAP1 expression is upregulated by loss of RB1 in prostate cancer cells. The Prostate 39 25585568
1996 RB [corrected] as a modulator of transcription. Biochimica et biophysica acta 39 8764839
2010 Regulation of RB transcription in vivo by RB family members. Molecular and cellular biology 38 20100864
2006 Rb, whi it's not just for metazoans anymore. Oncogene 38 16936741
2011 Rb1 gene inactivation expands satellite cell and postnatal myoblast pools. The Journal of biological chemistry 35 21478154
2007 Molecular genetics of RB1--the retinoblastoma gene. Seminars in ophthalmology 35 18097988
2006 Involvement of RB gene family in tumor angiogenesis. Oncogene 35 16936754
2017 Bidirectional transcription of Linc00441 and RB1 via H3K27 modification-dependent way promotes hepatocellular carcinoma. Cell death & disease 34 28300839
2016 Dephosphorylation of the Retinoblastoma protein (Rb) inhibits cancer cell EMT via Zeb. Cancer biology & therapy 34 27645778
2006 Rb at the interface between cell cycle and apoptotic decisions. Current molecular medicine 34 17100597
2002 Active RB elicits late G1/S inhibition. Experimental cell research 34 12027450
2022 Ginsenoside Rb1 Protects Against Diabetic Cardiomyopathy by Regulating the Adipocytokine Pathway. Journal of inflammation research 32 35023944
1996 Genes in the RB pathway and their knockout in mice. Seminars in cancer biology 32 9110405
2010 RB1CC1 activates RB1 pathway and inhibits proliferation and cologenic survival in human cancer. PloS one 31 20614030
2006 An E2F binding-deficient Rb1 protein partially rescues developmental defects associated with Rb1 nullizygosity. Molecular and cellular biology 31 16449662
1994 The role of the p53 and Rb-1 genes in cancer, development and apoptosis. Journal of cell science. Supplement 30 7883788
2010 Imprinting of RB1 (the new kid on the block). Briefings in functional genomics 29 20551090
2005 Alterations of the RB1 gene in dedifferentiated liposarcoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 29 15933756
2010 RB's original CIN? Genes & development 28 20551167
2009 RB1CC1 activates the promoter and expression of RB1 in human cancer. International journal of cancer 28 19437535
2004 Developmental defects in Rb-deficient retinae. Vision research 28 15536000
2000 Infrequent alternations of RB pathway (Rb-p16INK4A-cyclinD1) in adenoid cystic carcinoma of salivary glands. Anticancer research 27 10928172
1997 The retinoblastoma susceptibility gene RB-1 in multiple myeloma. Leukemia & lymphoma 27 9156653
2018 Comprehensive characterization of RB1 mutant and MYCN amplified retinoblastoma cell lines. Experimental cell research 26 30584916
2013 Rb1 family mutation is sufficient for sarcoma initiation. Nature communications 25 24150016
2011 RB regulates pancreas development by stabilizing Pdx1. The EMBO journal 25 21399612
2001 Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or Rb(6.15) translocation. Mammalian genome : official journal of the International Mammalian Genome Society 25 11845284
2024 Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis. Biochemical and biophysical research communications 24 38593619
2012 Effects of ginsenoside Rb₁ on skin changes. Journal of biomedicine & biotechnology 24 22505819
2021 Alterations in the RB Pathway With Inactivation of RB1 Characterize Glioblastomas With a Primitive Neuronal Component. Journal of neuropathology and experimental neurology 23 34850045
2020 Tumor Milieu Controlled by RB Tumor Suppressor. International journal of molecular sciences 23 32244804
2013 The origin of the RB1 imprint. PloS one 23 24282601
2012 Cooperation between Rb and Arf in suppressing mouse retinoblastoma. The Journal of clinical investigation 23 22484813
2023 Ginsenoside Rb1 for overcoming cisplatin-insensitivity of A549/DDP cells in vitro and vivo through the dual-inhibition on two efflux pumps of ABCB1 and PTCH1. Phytomedicine : international journal of phytotherapy and phytopharmacology 22 37087793
2018 Aspartate beta-hydroxylase promotes cholangiocarcinoma progression by modulating RB1 phosphorylation. Cancer letters 21 29733964
2016 SENP1-modulated sumoylation regulates retinoblastoma protein (RB) and Lamin A/C interaction and stabilization. Oncogene 21 27270425
1998 RB and apoptotic cell death. Frontiers in bioscience : a journal and virtual library 21 9545437
2015 Ras Regulates Rb via NORE1A. The Journal of biological chemistry 20 26677227
1998 Expression of the retinoblastoma tumor suppressor gene (RB-1) in acute leukemia. Leukemia & lymphoma 20 9517499

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