Affinage

RBL2

Retinoblastoma-like protein 2 · UniProt Q08999

Length
1139 aa
Mass
128.4 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBL2/p130 is a retinoblastoma family pocket protein that serves as the principal transcriptional repressor of cell-cycle genes in quiescent and early G1 cells, functioning as the core scaffold of the DREAM complex. In G0, p130 sequesters E2F4 and assembles with MuvB subunits (LIN-9, LIN-37, LIN-52, LIN-54, RBBP4) to occupy over 800 promoters, recruiting corepressors including HDAC1, Suv39H1, CtIP/CtBP, and BRM/SWI-SNF to silence E2F target genes through both histone-deacetylase-dependent and -independent mechanisms (PMID:17531812, PMID:10449734, PMID:15769944, PMID:28842672). Its activity is extinguished during cell-cycle entry by multi-site CDK4/6- and CDK2-dependent phosphorylation that disrupts E2F4 and MuvB binding, and by SCF(Skp2)-mediated ubiquitin–proteasomal degradation triggered by CDK4/6 phosphorylation of Ser672, while GSK3 phosphorylation stabilizes p130 in G0 and PP2A-mediated dephosphorylation restores its repressive capacity (PMID:11157749, PMID:12435635, PMID:15456871, PMID:15467457). Beyond G1/S gene repression, p130 directly inhibits cyclin A/E–CDK2 kinase activity through a conserved N-terminal domain, cooperates with p53 to repress G2/M genes after DNA damage and during senescence, and controls telomere length through interaction with RINT-1/Rad50 (PMID:9199292, PMID:31667499, PMID:16600870).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1993 High

    Identification of p130 as a new Rb-family pocket protein that binds CDK2 via D-type cyclins and viral oncoproteins established RBL2 as a growth-regulatory member of the pocket protein family.

    Evidence Yeast two-hybrid screen, in vitro binding, and co-immunoprecipitation in mammalian cells

    PMID:8253384

    Open questions at the time
    • Physiological role in cell cycle control not yet demonstrated
    • No knowledge of in vivo phosphorylation sites
    • Relationship to E2F transcription factors unknown
  2. 1993 High

    Discovery that p130 is the predominant E2F-associated protein in G0/early G1, with p107 replacing it near G1/S, established the cell-cycle-phase-specific division of labor among pocket proteins.

    Evidence Biochemical fractionation and DNA affinity chromatography across synchronized cell populations

    PMID:8253385

    Open questions at the time
    • Which E2F family member partners with p130 was not resolved
    • Whether p130-E2F complexes are repressive or merely sequestering was unclear
  3. 1996 High

    Demonstration that E2F-4 is the specific E2F partner sequestered by p130 in arrested cells, and that p130 and p107 show functional overlap but regulate distinct E2F target gene sets from pRB, defined the non-redundant transcriptional architecture of the Rb family.

    Evidence Specific antisera immunoprecipitation across cell cycle stages; gene expression in single and double knockout mouse cells

    PMID:8657117 PMID:8682294 PMID:9192872

    Open questions at the time
    • Mechanism of transcriptional repression (active versus passive) not resolved
    • Identity of additional cofactors unknown
  4. 1997 High

    Reconstitution of p130-mediated CDK2 inhibition with purified proteins revealed that p130 directly inhibits cyclin A/E–CDK2 kinase activity through its N-terminal domain, establishing a CDK-inhibitory function independent of E2F sequestration.

    Evidence In vitro kinase assays with recombinant p130, cyclin, and CDK2; mutagenesis; endogenous complex purification

    PMID:9199292

    Open questions at the time
    • Relative in vivo contribution of CDK inhibition versus E2F repression to growth arrest unknown
    • Structural basis of inhibition unresolved
  5. 1998 High

    Demonstration that p130 protein decline in proliferating cells is blocked by proteasome inhibitors and correlates with CDK-mediated phosphorylation revealed post-translational control of p130 abundance, linking phosphorylation to protein destruction.

    Evidence Proteasome inhibitors, cell synchronization, protein stability analysis

    PMID:9563849

    Open questions at the time
    • The ubiquitin ligase responsible was not identified
    • Specific phosphosites triggering degradation unknown
  6. 1999 High

    Identification of CtIP/CtBP as pocket-domain-interacting corepressors and of TFIIIB as a p130 target established that p130 actively represses both Pol II and Pol III transcription through distinct HDAC-independent mechanisms.

    Evidence Yeast two-hybrid, co-IP, transcriptional reporter assays, in vitro Pol III transcription, p107/p130 double-knockout fibroblasts

    PMID:10330166 PMID:10449734

    Open questions at the time
    • Whether Pol III repression occurs in vivo at specific loci unresolved
    • Full repertoire of corepressor complexes unknown
  7. 2001 High

    Comprehensive phosphosite mapping (22 sites) and mutagenesis showed that three CDK4/6-specific phosphorylations critically regulate p130 growth-restraining activity, with additional sites required for E2F-4 release, while CDK2 can independently drive p130 phosphorylation in pRB-null contexts.

    Evidence Mass spectrometry, extensive site-directed mutagenesis, cell cycle analysis, dominant-negative CDK2

    PMID:10906146 PMID:11157749 PMID:12006580

    Open questions at the time
    • Ordered sequence of phosphorylation events in vivo not resolved
    • Structural consequences of individual phosphorylations unknown
  8. 2001 High

    Chromatin-level studies demonstrated that p130-E2F4 imposes HDAC-independent, TSA-insensitive repression at E2F sites distinct from pRb-HDAC1-mediated repression at Sp1 sites, and that p130 shuttles between nucleus and cytoplasm via multiple NLS motifs.

    Evidence ChIP, trichostatin A treatment, GAL4 reporter assays, heterokaryon fusion, domain mapping

    PMID:11158299 PMID:11756542

    Open questions at the time
    • Functional significance of nuclear-cytoplasmic shuttling unclear
    • Chromatin remodeling cofactors at p130-bound loci not identified
  9. 2002 High

    Identification of SCF(Skp2) as the E3 ligase targeting p130 for ubiquitin-dependent degradation upon CDK4/6-mediated Ser672 phosphorylation resolved the mechanism coupling mitogenic signaling to p130 elimination during cell-cycle entry.

    Evidence In vitro ubiquitination with recombinant Skp2, site-directed mutagenesis of Ser672, proteasome inhibition

    PMID:12435635

    Open questions at the time
    • Whether additional ubiquitin ligases target p130 under different conditions unknown
    • Deubiquitinase(s) for p130 not identified
  10. 2004 High

    Discovery that PP2A maintains a dynamic dephosphorylation equilibrium with CDKs on p130/p107 throughout the cell cycle, and that GSK3 phosphorylation specifically stabilizes p130 in G0, completed the kinase/phosphatase regulatory circuit governing p130 activity and abundance.

    Evidence PP2A/CDK inhibitors, SV40 small-t expression, GSK3 inhibitors, phospho-specific antibodies, co-IP

    PMID:12621062 PMID:15456871 PMID:15467457

    Open questions at the time
    • Specific PP2A B-regulatory subunit mediating p130 dephosphorylation not identified
    • How GSK3 phosphorylation protects from proteasomal degradation mechanistically unresolved
  11. 2005 High

    p130-E2F4 was shown to recruit HDAC1 and Suv39H1 histone methyltransferase in neurons to silence pro-apoptotic genes, and p130/p107 were found to repress G2/M genes after DNA damage, broadening the functional scope of p130 beyond G1/S control to cell survival and G2 checkpoint maintenance.

    Evidence ChIP, co-IP, histone modification analysis in neurons; knockout MEFs with DNA damage

    PMID:15769944 PMID:15827088

    Open questions at the time
    • Full target gene repertoire in neurons not defined
    • Whether p130 recruits Suv39H1 directly or through E2F4 unclear
  12. 2006 High

    Identification of the p130–RINT-1–Rad50 complex revealed an unexpected role for p130 in controlling telomere length by suppressing recombination-based telomere elongation.

    Evidence Co-immunoprecipitation, knockdown, telomere length analysis

    PMID:16600870

    Open questions at the time
    • Whether this function is pocket-domain-dependent unknown
    • Mechanism by which p130 inhibits telomeric recombination not resolved
    • Generalizability beyond the cell types tested unclear
  13. 2007 High

    Biochemical purification and genomic mapping of the DREAM complex (p130–E2F4–DP–LIN-9/37/52/54/RBBP4) occupying >800 promoters in G0, with MuvB switching to B-Myb in S phase, unified p130's repressor functions into a single evolutionarily conserved multisubunit complex.

    Evidence Mass spectrometry proteomics, ChIP-chip, RNAi, co-IP

    PMID:17531812 PMID:17563750

    Open questions at the time
    • How CDK4 phosphorylation of p130 leads to MuvB release mechanistically unresolved
    • Structural basis of DREAM assembly unknown
  14. 2017 High

    Demonstration that p130-E2F4-HDAC1-BRM(SWI/SNF) occupies the PARP1 promoter in post-mitotic monocytes, deacetylating nucleosomes and compacting chromatin, extended DREAM-related repression to differentiation-specific gene silencing with defined chromatin remodeling.

    Evidence ChIP, co-IP, HDAC inhibitor treatment, siRNA knockdown of RBL2

    PMID:28842672

    Open questions at the time
    • Whether BRM is a general DREAM-associated remodeler or promoter-specific unknown
    • Genome-wide chromatin compaction by p130 in monocytes not profiled
  15. 2018 High

    Identification of AKT-mediated phosphorylation of p130 at Ser941 as a degradation signal added a PI3K/AKT input to p130 regulation, explaining how oncogenic AKT signaling eliminates p130 independently of CDK-Skp2.

    Evidence In vitro kinase assay, S941A mutagenesis, AKT inhibitor treatment, shRNA rescue

    PMID:29606701

    Open questions at the time
    • E3 ligase responsible for AKT-triggered p130 degradation not identified
    • Whether AKT and CDK pathways converge on the same degradation machinery unknown
  16. 2019 High

    Genome-wide expression profiling in RB-family knockout human fibroblasts after p53 activation revealed that p130 cooperates with RB to repress G1/S genes and with p107 to repress G2/M genes, clarifying the combinatorial logic of pocket protein function downstream of p53/p21.

    Evidence Gene expression profiling, DNA damage treatment, RB family knockout primary human fibroblasts

    PMID:31667499

    Open questions at the time
    • Whether DREAM versus non-DREAM complexes mediate the G2/M versus G1/S specificity not resolved
  17. 2020 High

    Genetic epistasis in a mouse SCLC model showed that RBL2 loss derepresses FGFR1 and that Fgfr1 knockout suppresses RBL2-loss-driven tumors, identifying a specific oncogenic effector pathway downstream of RBL2 inactivation.

    Evidence RBL2 restoration/knockdown with expression readout; conditional Fgfr1 knockout in SCLC mouse model

    PMID:32973083

    Open questions at the time
    • Whether FGFR1 is a direct DREAM target promoter not confirmed by ChIP
    • Generalizability to non-SCLC tumors unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of DREAM complex assembly, the identity of PP2A B-subunit(s) and deubiquitinase(s) specific to p130, whether nuclear-cytoplasmic shuttling has a regulatory function, and how DREAM versus non-DREAM p130 complexes achieve promoter-class specificity for G1/S versus G2/M targets.
  • No high-resolution structure of p130 alone or in DREAM
  • PP2A regulatory subunit specificity unknown
  • Mechanism of G1/S versus G2/M target gene selectivity unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 2 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 8 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2
Partners
E2F4HDAC1LIN37LIN52LIN54LIN9RBBP4RINT1
Complex memberships
DREAM complexp130-E2F4-HDAC1-BRM complexp130-RINT-1-Rad50 complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 RBL2/p130 was identified as a new Rb family member that interacts with CDK2 through a cyclin bridge in a two-hybrid screen, and binds to viral oncoproteins (SV40 large T antigen, adenovirus E1A) through its pocket domain; it shows a clear preference for D-type cyclins over other cyclins. Yeast two-hybrid screen, in vitro binding assays, co-immunoprecipitation Genes & development High 8253384
1993 p130 is the major E2F-associated protein in G0/early G1 cells, forming cell cycle-specific complexes with E2F; p130-E2F complexes associate with cyclin-cdk kinases including cyclin E-cdk2 in late G1, and p107 replaces p130 as the major E2F partner near the G1/S border. Biochemical fractionation, DNA affinity chromatography, immunoprecipitation, cell synchronization Genes & development High 8253385
1996 In quiescent mouse embryo fibroblasts lacking p130, much of the E2F activity that normally associates with p130 instead associates with p107, indicating functional overlap; combined loss of p130 and p107 causes deregulated chondrocyte growth and defective endochondral bone development, demonstrating their shared role in growth regulation. Gene targeting in mouse, mouse embryo fibroblast cultures, epistasis via double knockout Genes & development High 8682294
1996 E2F-4 accounts for the majority of endogenous E2F activity; in arrested cells E2F-4 is sequestered specifically by p130, and as cells pass the G1-to-S transition, E2F-4 associates with pRB and p107 instead. Specific antisera immunoprecipitation, cell synchronization, E2F complex characterization Molecular and cellular biology High 8657117
1996 pRB2/p130 overexpression induces G1 growth arrest that can be rescued by cyclins A, E, and D as well as E2F1 and E1A; p130 physically interacts with cyclins A and E throughout the cell cycle, and its associated kinase activity peaks near G1/S. Cell transfection, FACS analysis, co-immunoprecipitation, kinase assays Cancer research High 8616840
1995 p130 exists in multiple cell cycle-dependent phosphorylated forms; specific hypophosphorylated forms in G0/early G1 associate with E1A; p130 undergoes an abrupt shift to a hyperphosphorylated form in mid-G1 that persists throughout the remainder of the cell cycle, with associated histone H1 kinase activity peaking in late S/G2/M. Cell synchronization, in vitro E1A binding, histone H1 kinase assay, immunoprecipitation Oncogene High 7651744
1997 p107 and p130 use a conserved N-terminal domain to inhibit cyclin E-cdk2 and cyclin A-cdk2 kinase activity when bound stoichiometrically; endogenous p130-cyclin A-cdk2 complexes purified from human cells also display low kinase activity that is augmented by dissociation of p130, suggesting a direct CDK inhibitory mechanism. In vitro reconstitution with purified recombinant proteins, kinase assays, purification of endogenous complexes, mutagenesis Molecular and cellular biology High 9199292
1997 pRB and p107/p130 control different sets of E2F target genes: pRB loss deregulates one set, while combined loss of p107 and p130 deregulates a completely different set, demonstrating distinct and non-overlapping functions in E2F regulation. Gene expression analysis of primary cells from single and double knockout mice Genes & development High 9192872
1999 p130 (and pRB) interact with CtIP through the p130 pocket domain via an LXCXE motif on CtIP; CtIP in turn interacts with the corepressor CtBP, and this CtIP/CtBP complex mediates transcriptional repression; this constitutes a histone deacetylase-independent mechanism of E2F/p130-mediated repression. Yeast two-hybrid screen, co-immunoprecipitation, transcriptional repression assays, domain mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 10449734
2002 p130 degradation during cell cycle reentry is regulated by phosphorylation-dependent proteolysis: CDK4/6 phosphorylates p130 on Serine 672, which enables binding by the F-box protein Skp2 of the SCF(Skp2) ubiquitin ligase complex, leading to polyubiquitination and proteasomal degradation. In vitro binding assays with recombinant Skp2, in vitro ubiquitination assay, site-directed mutagenesis, proteasome inhibition, dominant-negative CDK expression Genes & development High 12435635
2001 p130 shuttles between the nucleus and cytoplasm; two C-terminal nuclear localization signals (NLS) and a functional NLS within the unique Loop region drive nuclear import, while an N-terminal domain confers cytoplasmic localization; the intact pocket domain is also sufficient for nuclear translocation. Heterokaryon fusion assay, transient transfection with reporter constructs, microinjection, domain mapping Molecular and cellular biology High 11756542
2001 p130 imposes a HDAC-independent, TSA-insensitive repression state on E2F sites (e.g., at the dhfr promoter) in quiescent cells, whereas pRb-mediated repression at Sp1 sites is TSA-sensitive; the p130-E2F4-DP complex cooperates with Sp1-pRb-HDAC1 complexes for stable repression during G0. Chromatin immunoprecipitation, co-immunoprecipitation, trichostatin A treatment, GAL4 fusion reporter assays Molecular and cellular biology High 11158299
2004 GSK3 phosphorylates p130 specifically during G0 arrest; GSK3-mediated phosphorylation contributes to p130 protein stability in quiescence but does not affect p130's ability to interact with E2F4 or cyclins. GSK3 small-molecule inhibitors, site-specific phospho-mutants of p130, phospho-specific antibodies, co-immunoprecipitation Molecular and cellular biology High 15456871
2003 Oxidative stress (H2O2) induces rapid dephosphorylation of pRb, p107, and p130 via protein phosphatase 2A (PP2A); PP2A core enzyme physically interacts with pRb and p107; SV40 small t antigen (which inhibits PP2A) prevents this dephosphorylation, and PP2A-mediated dephosphorylation is required for H2O2-induced inhibition of DNA synthesis. Phosphatase inhibitors (okadaic acid, calyculin A), SV40 small t antigen expression, co-immunoprecipitation, phosphatase activity assays The Journal of biological chemistry High 12621062
2004 The overall phosphorylation state of p130 (and p107) is determined by a dynamic equilibrium between CDKs and PP2A; PP2A catalytic subunit specifically interacts with p130 and p107 throughout the cell cycle; pharmacological CDK inhibition rapidly leads to PP2A-mediated dephosphorylation of pocket proteins. Cycloheximide and flavopiridol treatment, PP2A inhibitors, SV40 small t antigen expression, co-immunoprecipitation Cell cycle High 15467457
2007 p130 forms a multisubunit complex called DREAM (DP, RB-like, E2F4, and MuvB) with mammalian MuvB proteins (LIN-9, LIN-37, LIN-52, LIN-54, RBBP4/LIN-53) and E2F4; DREAM binds to over 800 human promoters in G0 and is required for repression of E2F target genes; in S phase, MuvB dissociates from p130 and associates with MYB instead. Mass spectrometry proteomics, ChIP-chip genomics, RNAi knockdown, co-immunoprecipitation, bioinformatics Molecular cell High 17531812
2007 Mammalian LIN-9/Mip interacts with the p107 or p130/E2F4 repressor complex in a cell cycle-phase-dependent manner in G0/early G1; phosphorylation of pocket proteins by CDK4 disrupts LIN-9 binding; in late G1/S, LIN-9 instead associates with B-Myb; expression of p107 blocks B-Myb/LIN-9-mediated cyclin B promoter activation. Co-immunoprecipitation, cell cycle synchronization, promoter reporter assays Oncogene High 17563750
2001 p130 imposes a G1 block in hematopoietic cells in a manner dependent on its E2F-binding pocket domain but not the cyclin-binding domain; E2F-4 potentiates mitogenic response and its constitutive overexpression renders cells cytokine-independent, indicating a p130-E2F4 axis controls proliferation in these cells independently of pRB. Conditional expression, domain mutant analysis, retroviral overexpression, cell growth assays Proceedings of the National Academy of Sciences of the United States of America High 9671719
2001 In 22 phosphorylation sites of p130 identified in vivo, three CDK4/6-specific phosphorylations are critical for controlling growth-restraining activity; the CDK4-specific phosphorylation-deficient mutant (p130ΔCdk4) imposes a more sustained G1 arrest than constitutively active pRb; growth suppression involves cooperative effects of phosphorylation-regulated E2F binding and phosphorylation-independent sequestration of cyclin E/A-CDK2 through the N-terminal cyclin-binding motif. Mass spectrometry, site-directed mutagenesis, cell cycle analysis in U2OS cells, E2F reporter assays The EMBO journal High 11157749
2002 Six additional phosphorylation residues in p130 (Ser413, 639, 662, 1044, 1080, 1112) beyond the three CDK4-specific sites are necessary and sufficient for regulation of E2F-4 and cell cycle control; CDK4-specific sites on p107 are sufficient for E2F-4 regulation, revealing distinct phosphorylation mechanisms between p107 and p130. Extensive site-directed mutagenesis, E2F reporter assays, cell cycle analysis The Journal of biological chemistry High 12006580
2000 In pRB-negative, p16INK4A-positive cells, p130 is phosphorylated and released from E2F-4 through a CDK2-dependent (not CDK4/6-dependent) process; dominant-negative CDK2 prevents p130 phosphorylation, p130-E2F-4 dissociation, and E2F-4-dependent transcription. Cell cycle synchronization, dominant-negative CDK2 expression, immunoprecipitation, transcription reporter assays The Journal of biological chemistry High 10906146
2005 p130 is the predominant Rb family member associated with E2F in neurons; p130-E2F4 complex recruits HDAC1 and Suv39H1 to silence pro-apoptotic genes and promote neuron survival; apoptotic stimuli induce p130 hyperphosphorylation, dissociation of the p130-E2F4-Suv39H1-HDAC complex, altered H3 histone modification, and gene derepression leading to neuron death. Co-immunoprecipitation, ChIP, knockdown/overexpression, histone modification analysis Genes & development High 15769944
2005 p130 and p107 play a key role in transcriptional repression of G2/M genes (including plk1) in response to DNA damage; all three RB family proteins contribute to stable G2 arrest; loss of p130 and p107 partially abrogates repression of G2/M genes. Knockout mouse cells, gene expression analysis, DNA damage treatment, cell cycle analysis Journal of cell science High 15827088
2006 p130 interacts specifically with RINT-1 (a Rad50-interacting protein), and both p130 and RINT-1 are essential for controlling telomere length; p130 through RINT-1 forms a complex with Rad50, blocking telomerase-independent (recombination-based) telomere lengthening in normal cells. Co-immunoprecipitation, knockdown experiments, telomere length analysis Molecular cell High 16600870
1999 p107 and p130 repress RNA polymerase III transcription both in transfection assays and when added to cell extracts; they physically interact with a subunit of TFIIIB (the Pol III transcription factor), and disruption of this interaction by HPV E7 or in p107/p130 double-knockout fibroblasts deregulates Pol III activity. Pulldown assays, co-immunoprecipitation, transient transfection reporter assays, in vitro transcription with cell extracts, knockout mouse fibroblasts Molecular and cellular biology High 10330166
1998 Control of p130 accumulation is posttranscriptional; the decline of p130 protein in proliferating cells coincides with CDK-mediated phosphorylation and is blocked by 26S proteasome inhibitors, revealing ubiquitin-proteasome-dependent regulation of p130 stability. Proteasome inhibitors, cell cycle synchronization, protein stability analysis, northern blotting Cell growth & differentiation High 9563849
2000 p130 is an essential mediator of Bcl-2-induced retardation of cell cycle entry; Bcl-2 elevates p130 levels and maintains repressive p130-E2F4 complexes; this delays E2F1 accumulation during G1 progression, and overexpression of E2F1 overrides Bcl-2 inhibition. Bcl-2 overexpression in p130 and p27 knockout cells, E2F4 co-expression, cell cycle analysis Molecular and cellular biology High 10848600
2018 RBL2/p130 is a direct substrate of AKT kinase; AKT1 physically interacts with RBL2/p130 and phosphorylates it on Ser941 within the pocket domain; pharmacological AKT inhibition impairs Ser941 phosphorylation, increases p130 stability, nuclear levels, and mRNA expression, and triggers p130-dependent apoptosis in cancer cells. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (S941A), AKT inhibitor treatment, shRNA knockdown Oncogene High 29606701
2019 Upon p53 activation by DNA damage, p130 and RB cooperate to repress G1/S genes, while p130 and p107 specifically repress G2/M genes; repression of G2/M genes by p107 and p130 reduces mitotic entry, revealing distinct roles for each RB family member in p53/p21-mediated cell cycle arrest. Gene expression profiling of primary human fibroblasts, DNA damage treatment, RB family knockout cells Nucleic acids research High 31667499
2010 KSHV miRNA K12-4-5p targets RBL2/p130; ectopic expression of this miRNA reduces RBL2 protein and increases DNMT1, DNMT3a, and DNMT3b mRNA levels, indicating that RBL2/p130 represses DNMT3a/3b transcription and KSHV exploits this pathway to maintain viral latency through epigenetic regulation. miRNA transfection, western blotting, RT-qPCR, miRNA target analysis Journal of virology Medium 20071580
2008 miR-17-92 cluster directly targets the 3' UTR of Rb2/p130 mRNA as demonstrated by luciferase reporter assay, reducing p130 levels during preadipocyte clonal expansion and promoting adipocyte differentiation; siRNA knockdown of p130 recapitulates miR-17-92 overexpression phenotype. Luciferase 3' UTR reporter assay, stable transfection, siRNA knockdown, triglyceride accumulation assay Proceedings of the National Academy of Sciences of the United States of America High 18287052
2017 RBL2/p130 interacts with E2F4 and binds to promoter regions of E2F target genes to repress them; miR-17-5p directly targets RBL2, disrupting the RBL2/E2F4 repressor complex and shifting E2F activity from repression to activation, leading to cell cycle entry and proliferation in pancreatic cancer cells. ChIP, co-immunoprecipitation, miRNA overexpression, luciferase reporter assay, cell cycle analysis Cancer letters High 28987387
2006 p53 cooperates selectively with p130 (Rb2) to induce cellular senescence; p53 activation induces a switch in pocket protein expression from pRb/p107 to p130, which then represses cyclin A to maintain G1/S arrest; inactivation of p53 in senescent cells restores pRb/p107, and the arrest is maintained by p130-dependent repression. Temperature-sensitive p53 mutant system, protein expression analysis, cell cycle analysis, protein knockdown Cell death and differentiation High 16123778
2010 Androgens repress EZH2 expression through a pathway requiring functional androgen receptor and both the retinoblastoma protein and p130; this mechanism mediates upregulation of EZH2 target genes and affects cell migration. Androgen treatment, castration in xenograft model, knockdown experiments, gene expression analysis Endocrinology Medium 20881251
2020 RBL2 loss induces FGFR1 expression, and restoration of RBL2 represses FGFR1, suggesting RBL2 acts as a transcriptional repressor of FGFR1; in a mouse model of SCLC, Fgfr1 knockout suppresses tumor development driven by Rbl2 loss but not in wild-type Rbl2 tumors. RBL2 restoration/knockdown with gene expression readout, mouse genetic model, Fgfr1 conditional knockout Cancer research High 32973083
2017 RBL2/p130 forms an E2F4-RBL2-HDAC1-BRM(SWI/SNF) repressor complex at the PARP1 promoter in post-mitotic monocytes; this complex deacetylates nucleosomes and compacts chromatin to repress PARP1 transcription; silencing RBL2 in monocytes restores PARP1 expression and increases transcription of pluripotency factors. ChIP, co-immunoprecipitation, HDAC inhibitor treatment, RBL2 siRNA knockdown, gene expression analysis Scientific reports High 28842672
2000 p130 overexpression in myoblasts blocks both cell cycle progression and the differentiation program; p130 represses MyoD transactivation capacity, reducing MyoD levels, and thereby promotes a reserve cell fate during terminal muscle differentiation; this repression is abolished by co-transfection with pRB. Forced expression in C2 myoblasts, transcription reporter assays, FACS, immunostaining Current biology High 10801445

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Genes & development 474 8253384
1997 pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes & development 390 9192872
1993 Cell cycle-specific association of E2F with the p130 E1A-binding protein. Genes & development 373 8253385
1996 Shared role of the pRB-related p130 and p107 proteins in limb development. Genes & development 372 8682294
2007 Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence. Molecular cell 341 17531812
1996 E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. Molecular and cellular biology 313 8657117
2008 miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proceedings of the National Academy of Sciences of the United States of America 298 18287052
2002 The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2). Genes & development 244 12435635
2001 p107 and p130: versatile proteins with interesting pockets. Experimental cell research 198 11237530
1997 The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas. Nature medicine 179 9256285
1995 Adhesion-induced tyrosine phosphorylation of the p130 src substrate. Journal of cell science 171 7542255
2010 Epigenetic regulation of Kaposi's sarcoma-associated herpesvirus latency by virus-encoded microRNAs that target Rta and the cellular Rbl2-DNMT pathway. Journal of virology 170 20071580
1999 A mechanism for Rb/p130-mediated transcription repression involving recruitment of the CtBP corepressor. Proceedings of the National Academy of Sciences of the United States of America 162 10449734
2002 EphrinA1-induced cytoskeletal re-organization requires FAK and p130(cas). Nature cell biology 158 12134157
2013 The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis. Science signaling 149 24003254
1995 Cell cycle-dependent phosphorylation of the retinoblastoma-related protein p130. Oncogene 134 7651744
2000 Bcl-2 retards cell cycle entry through p27(Kip1), pRB relative p130, and altered E2F regulation. Molecular and cellular biology 129 10848600
1996 Rho stimulates tyrosine phosphorylation of focal adhesion kinase, p130 and paxillin. Journal of cell science 127 8743960
2012 Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130. Nature communications 125 23250421
2004 Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130. Genes & development 121 15574596
1992 Tyrosine-phosphorylated epidermal growth factor receptor and cellular p130 provide high affinity binding substrates to analyze Crk-phosphotyrosine-dependent interactions in vitro. The Journal of biological chemistry 119 1375224
1996 Activity of the retinoblastoma family proteins, pRB, p107, and p130, during cellular proliferation and differentiation. Critical reviews in biochemistry and molecular biology 116 8817077
2002 Role of the PLC-related, catalytically inactive protein p130 in GABA(A) receptor function. The EMBO journal 110 11867528
2003 Oxidative stress induces protein phosphatase 2A-dependent dephosphorylation of the pocket proteins pRb, p107, and p130. The Journal of biological chemistry 102 12621062
1997 p130 and p107 use a conserved domain to inhibit cellular cyclin-dependent kinase activity. Molecular and cellular biology 101 9199292
2007 Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex. Oncogene 99 17563750
2006 p130-angiomotin associates to actin and controls endothelial cell shape. The FEBS journal 95 16640563
1996 Functional analysis of pRb2/p130 interaction with cyclins. Cancer research 95 8616840
2000 Combinatorial roles for pRB, p107, and p130 in E2F-mediated cell cycle control. Proceedings of the National Academy of Sciences of the United States of America 92 10995475
1999 Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone. The Journal of biological chemistry 92 9988732
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