Affinage

Showing RBL1 — P107 is a alias.

RBL1

Retinoblastoma-like protein 1 · UniProt P28749

Length
1068 aa
Mass
120.8 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 46 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

RBL1 (p107) is a nuclear pocket protein that restrains cell proliferation through dual, mechanistically separable activities: transcriptional repression via E2F factors and direct stoichiometric inhibition of G1/S cyclin-dependent kinases (PMID:1833063, PMID:7743997). Through an RB-homologous pocket domain that independently binds SV40 large T antigen and adenovirus E1A, p107 assembles cell-cycle-regulated complexes with E2F-4 (and E2F-5) together with cyclin E/cdk2 in G1 and cyclin A/cdk2 in S phase, repressing E2F-dependent transcription and arresting sensitive cells in G1 (PMID:1531040, PMID:1530885, PMID:1532457, PMID:1532458, PMID:1398067, PMID:8319904, PMID:7958925, PMID:7958924, PMID:8657117). A unique spacer region distinguishes p107 from pRB: it harbors a p21-related cyclin/cdk2-binding domain that, together with an N-terminal site, inhibits cyclin A/cdk2 and cyclin E/cdk2 kinase activity with a Ki comparable to p21 — an inhibitory function pRB lacks (PMID:1532457, PMID:1532458, PMID:7622038, PMID:9199292, PMID:9710622). p107 activity is governed by phosphorylation: cyclin D1/cdk4 phosphorylates p107 at specific residues (Thr-369, Ser-640, Ser-964, Ser-975) in mid-G1, dissociating it from E2F-4 and releasing the growth block, while a PP2A holoenzyme (including the regulatory subunit PR59 and the C subunit) reverses this phosphorylation in response to oxidative, UV, and FGF stimuli to restore the repressive state (PMID:7797074, PMID:8643455, PMID:9927208, PMID:11884610, PMID:12621062, PMID:15467457). Beyond E2F, p107 directly binds and represses c-Myc, Sp1, and the TFIIIB subunit of the RNA polymerase III machinery, and acts as a TGFβ signal transducer within a Smad3/E2F4/DP1/p107 complex that translocates to the nucleus to repress c-myc (PMID:8076603, PMID:8146655, PMID:7565695, PMID:10330166, PMID:12150994). Genetically, p107 functions redundantly with p130 in endochondral bone development and as a tumor suppressor in the retina in a pRB-deficient background, and it controls differentiation programs by repressing Hes1 and Notch1 in neural progenitors and opposing pRB in adipocyte fate (PMID:8682294, PMID:8682293, PMID:9620848, PMID:15353549, PMID:17591923, PMID:16271529).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1991 High

    Established that p107 is a distinct RB-family member by defining a pocket domain capable of independently engaging viral oncoproteins, framing it as a candidate growth regulator separate from pRB.

    Evidence cDNA cloning, sequence analysis, and binding assays with SV40 large T antigen and adenovirus E1A

    PMID:1833063

    Open questions at the time
    • Cellular endogenous binding partners not yet identified
    • Functional consequence of pocket binding unknown at this stage
  2. 1992 High

    Resolved how p107 connects to the cell cycle by showing it forms temporally distinct E2F complexes — cyclin E/cdk2 in G1 and cyclin A/cdk2 in S phase — distinguishing it from the G1-phase RB–E2F complex.

    Evidence Co-immunoprecipitation, gel mobility shift, and cell cycle fractionation; cyclin E-specific antisera

    PMID:1398067 PMID:1530885 PMID:1531040 PMID:1532457 PMID:1532458

    Open questions at the time
    • Identity of the E2F partner not yet established as E2F-4
    • Functional output of cyclin binding undefined
  3. 1992 High

    Mapped cyclin A binding to the unique spacer between the pocket A/B sub-segments, revealing a structural feature absent from pRB that enables direct cyclin recruitment.

    Evidence In vitro binding assay with pocket domain mutants

    PMID:1532457 PMID:1532458

    Open questions at the time
    • Whether cyclin binding modulates kinase activity not yet tested
  4. 1993 High

    Demonstrated p107 is a functional E2F repressor and growth suppressor, and that its E1A-independent mutants still inhibit proliferation, establishing mechanistic divergence from pRB.

    Evidence Transient transfection reporter assays, proliferation and flow cytometry assays, Gal4-tethering, monoclonal antibody Co-IP

    PMID:7685208 PMID:8230483 PMID:8319904 PMID:8458319

    Open questions at the time
    • E2F partner identity still inferred as 62-65 kDa phosphoprotein
    • Cell-type specificity of repression unexplained
  5. 1994 High

    Identified E2F-4 as the specific p107 partner and c-Myc as a direct non-E2F target, broadening p107's repertoire beyond E2F to a second proliferation-driving transcription factor.

    Evidence Co-IP, reporter and transformation assays, growth rescue experiments

    PMID:7958924 PMID:7958925 PMID:8076603 PMID:8146655

    Open questions at the time
    • Promoter-level mechanism of c-Myc repression not defined
    • Relative contribution of E2F vs c-Myc repression to arrest unclear
  6. 1995 High

    Defined two independent growth-suppression domains — an E2F-binding pocket and a p21-related cyclin/cdk2-inhibitory spacer — establishing p107 as a direct CDK inhibitor whose binding is mutually exclusive with p21.

    Evidence In vitro kinase inhibition, competitive binding, deletion mutant growth assays, DNA damage treatment

    PMID:7622038 PMID:7743997 PMID:7799940 PMID:8668177

    Open questions at the time
    • Precise cyclin-binding residues not yet mapped
    • In vivo significance of CDK inhibition vs E2F repression not resolved
  7. 1995 High

    Showed that cyclin D1/cdk4 (not cyclin E/cdk2) phosphorylates p107 in mid-G1 to dissociate it from E2F-4 and inactivate its G1 block, establishing the upstream switch controlling p107 activity.

    Evidence In vivo phosphorylation, dominant-negative cdk4, Co-IP, cell synchronization

    PMID:7797074 PMID:8643455

    Open questions at the time
    • Specific phosphorylation sites not yet identified
    • Reversal/dephosphorylation mechanism unknown
  8. 1995 Medium

    Extended p107's repressive reach to Sp1 and defined an E2F-dependent autoregulatory loop at its own promoter, showing distinct domains for distinct transcription-factor targets.

    Evidence Endogenous Co-IP, Gal4-Sp1 reporter assays, promoter deletion and site-directed mutagenesis

    PMID:7565695 PMID:7791762

    Open questions at the time
    • Physiological role of Sp1 repression unclear
    • Autoregulatory loop tested only in reporter context
  9. 1996 High

    Provided the in vivo genetic framework: p107 is dispensable alone but redundant with p130 in chondrocyte/bone development and overlapping with pRB, with combined loss causing lethality and dysplasia.

    Evidence Single and compound knockout mice, histology, MEF analysis, E2F partner-switching immunoprecipitation survey

    PMID:8657117 PMID:8682293 PMID:8682294

    Open questions at the time
    • Molecular basis of functional redundancy with p130 not dissected
    • Tissue-specific target genes undefined
  10. 1997 High

    Expanded p107 function to RNA Pol III repression via TFIIIB and rigorously confirmed stoichiometric CDK inhibition through a conserved N-terminal domain, separating it from E2F binding.

    Evidence In vitro reconstitution with purified proteins, pull-down, endogenous complex purification, double-KO MEFs

    PMID:10330166 PMID:8627752 PMID:9199292 PMID:9271376

    Open questions at the time
    • Physiological signals coupling p107 to Pol III regulation unclear
  11. 1998 High

    Quantified p107 as a dual cyclin/cdk2 inhibitor with two cyclin-binding sites of distinct function, and demonstrated it acts as a tumor suppressor in the retina in a pRB-null background.

    Evidence In vitro Ki determination, domain mutant analysis, peptide competition, chimeric mouse histopathology

    PMID:9563849 PMID:9620848 PMID:9710622

    Open questions at the time
    • Human retinoblastoma relevance not directly established
    • Tissue restriction of tumor suppression unexplained
  12. 1999 High

    Identified PP2A (via the PR59 regulatory subunit) and C/EBPalpha as p107-specific regulators, defining the phosphatase that reactivates p107 and a differentiation-linked complex disruptor.

    Evidence Yeast two-hybrid, Co-IP, dephosphorylation and cell cycle assays, EMSA disruption with purified C/EBPalpha

    PMID:10082561 PMID:9927208

    Open questions at the time
    • PP2A targeting specificity to p107 vs p130 not fully defined
    • In vivo role of PR59 untested
  13. 2002 High

    Mapped the four cyclin D1/cdk4 phosphorylation sites and revealed a TGFβ signal-transduction role, positioning p107 within a cytoplasmic Smad3/E2F4/DP1 complex that represses c-myc upon nuclear translocation.

    Evidence In vitro kinase assay with site-directed mutagenesis, phosphopeptide mapping, Co-IP, fractionation, ChIP, reporter assays

    PMID:11884610 PMID:12150994

    Open questions at the time
    • Coordination between CDK phosphorylation and TGFβ complex assembly unresolved
    • Generality of Smad-E2F site beyond c-myc unclear
  14. 2003 High

    Established stress-responsive PP2A-mediated p107 dephosphorylation as a route to growth arrest, with PP2A physically bound to p107 and activated by oxidative and UV stress.

    Evidence Co-IP, phosphatase inhibitor and SV40 small t experiments, in vitro dephosphorylation, p53/p21-null fibroblasts

    PMID:12621062 PMID:15467457 PMID:9989818

    Open questions at the time
    • Specific PP2A regulatory subunit for stress responses not pinned down
    • Signal relay from stress sensor to PP2A unknown
  15. 2004 Medium

    Placed p107 (with p130) as a critical effector of FGF growth inhibition in chondrocytes and as a repressor of Notch1 controlling neural stem cell self-renewal, linking it to differentiation-stage decisions.

    Evidence Compound knockout mice, chondrocyte/metatarsal organ culture, neurosphere assays, BrdU labeling, ChIP

    PMID:12177046 PMID:15353549

    Open questions at the time
    • Direct chondrocyte target genes of p107 undefined
    • Mechanism coupling FGF to p107 dephosphorylation not detailed
  16. 2005 Medium

    Connected p107 to the SCF-Skp2/p27 axis and to G2/M gene repression after DNA damage, and revealed it opposes pRB in adipocyte fate by indirect regulation of PGC-1alpha.

    Evidence Knockout and overexpression fibroblasts, Skp2 rescue, p27 stability and BrdU assays, gene expression profiling, ChIP on PGC-1alpha promoter

    PMID:15631990 PMID:15827088 PMID:16271529

    Open questions at the time
    • Whether p107 directly regulates Skp2 transcription unclear
    • p107 effect on adipose appears indirect via pRB
  17. 2007 Medium

    Defined p107 as a subunit of cell-cycle-phase-specific LIN-9/MuvB-containing complexes with E2F4 and as a repressor at Hes1, mechanistically linking it to G2/M gene control and neuronal commitment.

    Evidence Co-IP across cell cycle, reporter assays, ChIP at Hes1, genetic compound mutant rescue, neuronal birthdating

    PMID:17563750 PMID:17591923

    Open questions at the time
    • Full composition of the p107-MuvB complex not enumerated
    • Direct vs indirect Hes1 regulation in vivo not fully separated
  18. 2013 Medium

    Revealed a context-dependent reversal of p107 function: MAGE-A11 stabilizes p107 and converts it into a transcriptional co-activator of E2F1 in prostate cancer cells.

    Evidence Co-IP, ubiquitination assay, siRNA knockdown, reporter assays

    PMID:23853093

    Open questions at the time
    • Single lab; structural basis of the activator switch unknown
    • Physiological prevalence of this mode beyond high-MAGE-A11 tumors unclear
  19. 2019 Medium

    Refined the DREAM-complex model showing p107 cooperates with p130 to specifically repress G2/M genes after p53 activation, distinct from pRB/p130 repression of G1/S genes.

    Evidence Genome-wide expression profiling in primary human fibroblasts with RB-family knockdowns and DNA damage

    PMID:31667499

    Open questions at the time
    • Direct DREAM subunit interactions of p107 not biochemically resolved here
    • Determinants of G2/M vs G1/S target selectivity unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs (CDK phosphorylation, PP2A dephosphorylation, MAGE-A11 stabilization, TGFβ/FGF signaling) are integrated to switch p107 between repressor and activator states across tissues remains unresolved.
  • No unified structural model of phospho-regulated p107 states
  • Tissue-specific target gene maps incomplete
  • Human disease relevance beyond mouse retinoblastoma underexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 7 R-HSA-1266738 Developmental Biology 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 2
Partners
CCNA2CCND1CCNE1CDK2E2F4MYCPPP2CASP1
Complex memberships
DREAM complexLIN-9/MuvB complexSmad3–E2F4/5–DP1–p107 complexp107–E2F4–cyclin/cdk2 complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 p107 (RBL1) was cloned and shown to contain a major region of RB homology (~564 residues) that constitutes a 'pocket' domain capable of independently binding SV40 large T antigen and adenovirus E1A. The unique spacer sequence between the A and B sub-segments of the p107 pocket distinguishes it from RB. cDNA cloning, sequence analysis, binding assays with T antigen and E1A Cell High 1833063
1992 p107 forms a cell cycle-regulated complex with E2F and cyclin A during S phase, distinct from the G1-phase RB–E2F complex. This S-phase complex also contains p33cdk2. Co-immunoprecipitation, gel mobility shift assay, cell cycle fractionation Cell High 1530885 1531040 1532457 1532458
1992 Cyclin A binds directly to the p107 pocket domain (specifically the unique spacer sequence between the A and B sub-segments) in the absence of viral oncoproteins; this interaction does not occur with the RB pocket. In vitro binding assay, domain mapping with pocket mutants Science High 1532457 1532458
1992 Cyclin E and its associated cdk2 form a complex with E2F and p107 specifically during G1, whereas the cyclin A/cdk2/p107/E2F complex is S-phase specific, demonstrating temporally distinct cyclin partnerships for p107. Immunoprecipitation with cyclin E-specific antisera, cell cycle synchronization Genes & development High 1398067
1993 p107 is a potent inhibitor of E2F-mediated transactivation; overexpression of p107 arrests sensitive cells in G1. Growth arrest by p107 and pRB is rescued differentially by cell cycle regulators, and certain p107 mutants unable to associate with E1A still inhibit proliferation, indicating mechanistic differences from pRB. Transient transfection, reporter assay, cell proliferation assay, flow cytometry Genes & development High 8319904
1993 p107 inhibits E2F-dependent transcription in a co-transfection assay, and this repression correlates with the appearance of p107-containing E2F complexes at the G1/S transition rather than earlier in G1 like RB. Co-transfection reporter assay, EMSA, co-immunoprecipitation The EMBO journal High 8458319
1993 p107 associates in vivo with cyclin A, cyclin E, cdk2, and a 62–65 kDa E2F-like phosphoprotein (subsequently identified as E2F-4) that is immunologically distinct from pRB-associated E2F-1. Monoclonal antibody immunoprecipitation, biochemical characterization Journal of virology High 8230483
1993 p107 functions as a general transcriptional repressor when tethered to a promoter via E2F, and this repression is overcome by adenovirus E1A. Repression is cell-type-specific (absent in F9 embryonal carcinoma cells, present in differentiated derivatives). Transient co-transfection reporter assay, Gal4 fusion constructs Molecular biology of the cell Medium 7685208
1993 HPV16 E7 binds p107 in vivo through sequences overlapping but not identical to the RB-binding region, and this interaction is associated with a histone H1 kinase activity restricted to G2/M phase. Co-immunoprecipitation, kinase assay, E7 point mutant analysis Journal of virology Medium 8386265
1994 E2F-4 is a specific binding partner of p107 in vivo; p107 binding regulates E2F-4 transcriptional activity and suppresses the ability of E2F-4 to transform immortalized rodent cells. Co-immunoprecipitation, reporter assay, transformation assay Genes & development High 7958924 7958925
1994 p107 binds directly to the N-terminal transactivation domain of c-Myc in vivo and suppresses c-Myc-mediated transactivation; expression of c-Myc releases cells from p107-induced growth arrest but not pRB-induced arrest. Co-immunoprecipitation, reporter transactivation assay, cell growth rescue experiment The EMBO journal High 8076603 8146655
1995 p107 contains a p21CIP1-related cyclin/cdk2-binding domain (spacer region) that inhibits phosphorylation of target substrates by cyclin A/cdk2 and cyclin E/cdk2; binding of p107 and p21 to cyclin/cdk2 is mutually exclusive. DNA damage-elevated p21 displaces p107 from cyclin/cdk2 complexes. Activation of p107-bound cyclin/cdk kinases leads to dissociation of p107 from E2F. In vitro kinase inhibition assay, competitive binding, co-immunoprecipitation, DNA damage treatment Genes & development High 7622038
1995 p107 contains two independent growth suppression domains: one mediating E2F interaction and one mediating cyclin A/E-cdk2 interaction. In C33A cells, only the cyclin-binding domain is active as a growth suppressor, revealing a functional difference from pRB. Structure-function analysis with deletion mutants, co-expression growth assay The EMBO journal High 7743997
1995 Cyclin D1/cdk4, but not cyclin E/cdk2, phosphorylates p107 in vivo beginning ~8 hours after serum stimulation; phosphorylation by cyclin D1/cdk4 causes loss of p107 association with E2F-4 and release of the p107-induced cell cycle block. In vivo phosphorylation assay, dominant-negative cdk4 expression, co-immunoprecipitation, cell cycle analysis Genes & development High 7797074
1995 p107 phosphorylation begins in mid-G1 via cyclin D-associated kinase activity; hypophosphorylated p107 selectively binds E2F-4, and G1 cyclin-dependent phosphorylation of p107 dissociates p107–E2F-4 complexes and inactivates p107's G1 blocking function. Cell synchronization, phosphorylation timing analysis, co-immunoprecipitation, cell cycle block assay Proceedings of the National Academy of Sciences of the United States of America High 8643455
1995 p107's ability to suppress E2F-dependent transcription requires E2F binding but does not require association with cyclin A/cdk2; both E2F-dependent and E2F-independent events correlate with p107-mediated growth suppression. p107 mutant analysis, reporter assay, growth suppression assay Molecular and cellular biology Medium 7799940
1995 p107 associates with transcription factor Sp1 in vivo and represses Sp1-dependent transcription; this repression is mediated through a region of p107 distinct from the pocket domain required for E2F regulation. Co-immunoprecipitation from multiple cell lines, reporter assay with Gal4-Sp1 chimera, domain mapping Molecular and cellular biology Medium 7565695
1995 The p107 promoter contains tandem E2F binding sites; the retinoblastoma protein and p107 itself repress p107 promoter activity through the 5' (distal) E2F site, while the 3' (proximal, initiation-site) copy is more important for basal activity. This defines an autoregulatory loop. Promoter deletion analysis, site-directed mutagenesis, reporter assay, co-transfection Molecular and cellular biology Medium 7791762
1996 E2F-4 switches from p130 (in G0/quiescence) to association with p107 and pRB as cells re-enter the cell cycle at the G1-to-S transition; E2F-1, -2, and -3 bind only pRB and are restricted to post-G1/S; E2F-4 accounts for the vast majority of endogenous E2F activity. Immunoprecipitation with specific antisera, EMSA, cell synchronization Molecular and cellular biology High 8657117
1996 p107 and p130 have redundant roles in limb development: simultaneous genetic inactivation of both p107 and p130 causes deregulated chondrocyte growth, defective endochondral bone development, and neonatal lethality, while single knockouts are largely normal. Gene targeting in mouse, histological analysis, MEF culture analysis Genes & development High 8682294
1996 Targeted disruption of mouse p107 alone produces viable, fertile mice with no obvious abnormalities; combined Rb+/-;p107-/- mice show growth retardation and retinal dysplasia; Rb-/-;p107-/- embryos die ~2 days earlier than Rb-/- embryos with accelerated apoptosis in liver and CNS, demonstrating overlapping functions of p107 and Rb in vivo. Homologous recombination gene targeting, compound mutant generation, histological analysis Genes & development High 8682293
1996 p107 pocket domain is sufficient for E2F inactivation, general transcriptional repressor activity, and most growth suppressor activity; the A and B sub-domains of the pocket are fully functional even when expressed as separate proteins, suggesting they interact at the promoter. Deletion mutagenesis, Gal4-fusion reporter assay, co-expression growth assay Molecular and cellular biology Medium 8668177
1997 p107 and p130 repress RNA polymerase III transcription by directly interacting with the TFIIIB subunit of the Pol III transcription machinery; disruption by HPV E7 or genetic loss of p107/p130 deregulates Pol III activity. Transient transfection assay, pull-down with recombinant proteins, co-immunoprecipitation, cofractionation, MEFs from double-knockout mice Molecular and cellular biology High 10330166
1997 p107 and p130 use a conserved N-terminal domain (distinct from the E2F-binding pocket) to stoichiometrically inhibit cyclin A-cdk2 and cyclin E-cdk2 kinase activity in vitro; endogenous p130–cyclin A–cdk2 complexes purified from human cells display low kinase activity that is augmented upon dissociation of p130. In vitro reconstitution with purified recombinant proteins, kinase assay, purification of endogenous complexes Molecular and cellular biology High 9199292
1997 SV40 large T antigen alters the phosphorylation state of p107 and p130, requiring both the LXCXE domain (for binding) and the N-terminal J domain homology region; the J domain effect is separable from mere binding. Transient expression assay, phosphorylation state analysis, T antigen domain mutants Journal of virology Medium 8627752
1997 The J domain of SV40 large T antigen is required to inactivate p130 and p107; a heterologous DnaJ protein J domain functionally substitutes for T antigen's N terminus in altering p107/p130 phosphorylation; J domain is dispensable in MEFs lacking both p130 and p107, placing p107/p130 as the relevant J domain targets. Domain mutant and heterologous J domain substitution, phosphorylation analysis, MEFs from p107/p130 double-KO Molecular and cellular biology High 9271376
1998 p107 loss in a pRB-deficient background (p107/pRB double-null chimeric mice) leads to retinoblastoma, providing first in vivo evidence that p107 exerts a tumor suppressor function in the retina, suppressing retinoblastoma development caused by pRB deficiency. Gene targeting, chimeric mouse generation, histopathology Genes & development High 9620848
1998 p107 is a dual cyclin/cdk2 inhibitor with a Ki comparable to p21/WAF1; p107 harbors two cyclin-binding sites (N-terminal and C-terminal/spacer), both required for kinase inhibition. The C-terminal site is a substrate but not an inhibitor; the N-terminal site inhibits without being an efficient substrate. pRB does not inhibit cdks. In vitro kinase inhibition assay with Ki determination, domain mutant analysis, peptide competition Molecular and cellular biology High 9710622
1998 p107 expression is transcriptionally regulated in a growth-state-dependent manner via E2F-mediated repression in quiescent cells; p130 controls p107 expression in quiescent cells, whereas p130 protein stability is posttranscriptionally controlled by proteasomal degradation upon CDK-mediated phosphorylation. Northern blot, promoter analysis, proteasome inhibitor treatment, Western blot across growth states Cell growth & differentiation Medium 9563849
1999 A novel PP2A regulatory subunit PR59 specifically co-immunoprecipitates with p107 (but not pRB) and promotes dephosphorylation of p107 (but not pRB) when overexpressed, causing G1 accumulation; PR59 is a genuine PP2A component that targets the catalytic subunit specifically to p107. Yeast two-hybrid (isolation), co-immunoprecipitation, dephosphorylation assay, cell cycle analysis Oncogene High 9927208
1999 C/EBPalpha directly interacts with p107 (co-immunoprecipitation) and disrupts S-phase-specific E2F-p107 complexes through a protein-protein interaction mediated by a short C/EBPalpha domain with E2F homology, independent of C/EBPalpha DNA binding. Co-immunoprecipitation, EMSA, bacterially expressed purified C/EBPalpha disruption assay Molecular and cellular biology High 10082561
2000 p107 and pRB have opposing roles in adipocyte differentiation: pRB promotes differentiation and is required for cell cycle exit, while overexpression of p107 antagonizes differentiation; loss of p107 lowers the requirement for PPARgamma without affecting C/EBPalpha-driven transcription. Knockout fibroblasts, retroviral overexpression, reporter assay, adipogenesis assay Proceedings of the National Academy of Sciences of the United States of America Medium 10995476
2002 TGFβ signaling induces nuclear translocation of a preformed cytoplasmic complex containing Smad3, E2F4/5, DP1, and p107, which then associates with Smad4 to bind a composite Smad-E2F site on the c-myc promoter for transcriptional repression. p107 acts as a TGFβ signal transducer upstream of CDK in this context. Co-immunoprecipitation, subcellular fractionation, chromatin immunoprecipitation, reporter assay, cytoplasmic/nuclear complex characterization Cell High 12150994
2002 Cyclin D1/Cdk4 directly phosphorylates p107 at four specific sites (Thr-369, Ser-640, Ser-964, Ser-975) identified by in vitro kinase assay; these are not efficiently phosphorylated by Cdk2. The RXL motif of p107 facilitates Cdk4-mediated phosphorylation of nonconsensus sites. Nonphosphorylatable p107 at these four sites is not inactivated by cyclin D1/Cdk4 co-expression. In vitro kinase assay, site-directed mutagenesis, cell cycle arrest reversal assay, phosphopeptide mapping Molecular and cellular biology High 11884610
2002 FGF signaling causes rapid dephosphorylation of p107 and p130 (but not pRB) to induce G1 arrest in chondrocytes; p107-/-;p130-/- chondrocytes do not respond to FGF-mediated growth inhibition, while pRB-null chondrocytes respond normally, placing p107 and p130 as critical effectors of FGF growth inhibition. Genetic epistasis with single and compound knockout mice, chondrocyte micromass culture, metatarsal organ culture, viral oncoprotein rescue assay The Journal of cell biology High 12177046
2003 Oxidative stress (H2O2) induces rapid hypophosphorylation of p107 via PP2A activity: PP2A catalytic subunit physically interacts with p107 in both untreated and H2O2-treated cells; okadaic acid/calyculin A prevent dephosphorylation; SV40 small t (PP2A inhibitor) blocks this response; PP2A-mediated dephosphorylation of p107 contributes to DNA-synthesis inhibition. Co-immunoprecipitation of PP2A with p107, phosphatase inhibitor treatment, SV40 small t expression, phosphorylation analysis The Journal of biological chemistry High 12621062
2004 PP2A catalytic subunit specifically interacts with p107 and p130 throughout the cell cycle; PP2A activity, not PP1, is responsible for pocket protein dephosphorylation upon CDK inhibition; the balance between CDK and PP2A activities determines the overall phosphorylation state of p107. Co-immunoprecipitation of PP2A/C with p107, okadaic acid dose-response, SV40 small t expression, flavopiridol and cycloheximide treatments Cell cycle High 15467457
2004 UV irradiation induces rapid dephosphorylation of p107 via a PP2A-like phosphatase, increasing p107/E2F repressor complexes; this is independent of p53 and p21, and occurs with PP2A overexpression in vitro; specific PP2A B subunit overexpression interferes with UV-mediated p107 dephosphorylation. Phosphatase inhibitor assays, PP2A B-subunit overexpression, in vitro dephosphorylation with PP2A, p53/p21 null fibroblasts Oncogene Medium 9989818
2004 Adult p107-null mice have elevated neural stem/progenitor cell numbers in the lateral ventricles with enhanced self-renewal capacity; p107 represses Notch1 expression as shown by chromatin immunoprecipitation and overexpression experiments, placing p107 upstream of Notch1 in neural stem cell regulation. Neurosphere assay, BrdU labeling, in vivo progenitor ablation/repopulation, chromatin immunoprecipitation, p107 overexpression The Journal of cell biology Medium 15353549
2005 p107 promotes G1-to-S inhibition by downregulating expression of the F-box protein Skp2, leading to p27 stabilization; ectopic Skp2 restores p27 degradation and S phase entry in p107-overexpressing cells, and Skp2 inactivation abrogates p107's inhibitory effect on S phase. p107 overexpression and knockout fibroblasts, Skp2 ectopic expression, p27 stability assay, S phase entry (BrdU) The Journal of cell biology Medium 15631990
2005 p107 and p130 (but not pRB) play key roles in transcriptional repression of >20 G2/M genes in response to DNA damage; loss of p107 and p130 partially abrogates repression of PLK1 and other G2/M targets; mice lacking all three RB family proteins fail to accumulate at 4N DNA content after adriamycin treatment. Gene expression profiling, RB-family knockout MEFs and mouse cells, DNA damage treatment Journal of cell science Medium 15827088
2005 p107 loss in mice causes replacement of white adipose tissue with brown adipose tissue; WAT from p107-/- mice shows elevated PGC-1alpha and UCP-1; p107-/- precursors display downregulated pRB expression; chromatin IP shows pRB (not p107) binds the PGC-1alpha promoter to repress transcription. Knockout mouse analysis, ChIP showing pRb at PGC-1alpha promoter, adipocyte differentiation assay, Cre-mediated Rb deletion in primary preadipocytes Cell metabolism Medium 16271529
2007 Mammalian Mip/LIN-9 forms a cell-cycle-phase-specific complex with p107 (or p130) and E2F4 in G0/early G1; this complex is distinct from the Mip/LIN-9–B-Myb complex that forms in late G1/S. CDK4-mediated phosphorylation of p107 disrupts the Mip/LIN-9–p107 interaction. p107 expression blocks B-Myb/Mip/LIN-9-driven cyclin B promoter activation. Co-immunoprecipitation, cell cycle synchronization, reporter assay, phosphorylated p107 binding analysis Oncogene Medium 17563750
2007 p107 represses transcription at the Hes1 promoter; p107-null mice show enhanced Hes1 expression and reduced neuronal commitment; genetic reduction of Hes1 (single allele) in p107-null mice rescues neurosphere numbers and neurogenesis rate, placing p107 upstream of Hes1 in neural progenitor commitment. Chromatin immunoprecipitation at Hes1 promoter, neurosphere assay, genetic compound mutant, neuronal birthdating The Journal of cell biology Medium 17591923
2013 MAGE-A11 interacts physically with p107 (but not p130), stabilizes p107 by inhibiting its ubiquitination, and links p107 to hypophosphorylated E2F1, activating E2F1 transcriptional activity; in prostate cancer cells with high MAGE-A11, p107 acts as a transcriptional activator rather than repressor. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, reporter assay The Journal of biological chemistry Medium 23853093
2019 In response to p53 activation/DNA damage, p107 cooperates with p130 in the DREAM complex to repress G2/M cell cycle genes (not G1/S genes); pRB and p130 cooperate to repress G1/S genes; p107-DREAM and p130-DREAM repression of G2/M genes reduces mitotic entry. Gene expression profiling in primary human fibroblasts with RB family knockdowns, p53 activation by DNA damage Nucleic acids research Medium 31667499

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin A complex in a cell cycle-regulated manner. Cell 604 1531040
1993 Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. Genes & development 550 8319904
1991 Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell 459 1833063
1992 Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. Genes & development 456 1398067
2002 E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Cell 399 12150994
1997 pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes & development 390 9192872
1992 Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F. Nature 384 1530885
1996 Shared role of the pRB-related p130 and p107 proteins in limb development. Genes & development 373 8682294
1994 E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes & development 352 7958925
1994 E2F-4, a new member of the E2F transcription factor family, interacts with p107. Genes & development 345 7958924
1996 E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. Molecular and cellular biology 313 8657117
1996 Targeted disruption of p107: functional overlap between p107 and Rb. Genes & development 293 8682293
1998 Role of the retinoblastoma protein family, pRB, p107 and p130 in the negative control of cell growth. Oncogene 277 9916999
1993 Interactions of the p107 and Rb proteins with E2F during the cell proliferation response. The EMBO journal 255 8458319
1998 p107 is a suppressor of retinoblastoma development in pRb-deficient mice. Genes & development 252 9620848
1995 Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. Genes & development 252 7797074
1995 p107 uses a p21CIP1-related domain to bind cyclin/cdk2 and regulate interactions with E2F. Genes & development 248 7622038
2004 Cell-specific effects of RB or RB/p107 loss on retinal development implicate an intrinsically death-resistant cell-of-origin in retinoblastoma. Cancer cell 237 15193257
1992 Interaction of p107 with cyclin A independent of complex formation with viral oncoproteins. Science (New York, N.Y.) 229 1532457
1992 Interaction between human cyclin A and adenovirus E1A-associated p107 protein. Science (New York, N.Y.) 220 1532458
1994 Binding and suppression of the Myc transcriptional activation domain by p107. Science (New York, N.Y.) 218 8146655
1994 p130/pRb2 has growth suppressive properties similar to yet distinctive from those of retinoblastoma family members pRb and p107. Cancer research 215 7923196
2001 p107 and p130: versatile proteins with interesting pockets. Experimental cell research 198 11237530
1993 Human papillomavirus type 16 E7 associates with a histone H1 kinase and with p107 through sequences necessary for transformation. Journal of virology 195 8386265
2005 Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1alpha. Cell metabolism 181 16271529
1997 The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas. Nature medicine 179 9256285
1997 Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of simian virus 40 large T antigen. Molecular and cellular biology 157 9271376
1995 The pRB-related protein p107 contains two growth suppression domains: independent interactions with E2F and cyclin/cdk complexes. The EMBO journal 137 7743997
1994 Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation. The EMBO journal 137 8076603
2004 Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis. Development (Cambridge, England) 132 15148303
1994 HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of p107/E2F complexes. The EMBO journal 132 8112300
1997 Regulation and expression of retinoblastoma proteins p107 and p130 during 3T3-L1 adipocyte differentiation. The Journal of biological chemistry 124 9092557
2004 Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130. Genes & development 122 15574596
1998 Strain-dependent myeloid hyperplasia, growth deficiency, and accelerated cell cycle in mice lacking the Rb-related p107 gene. Molecular and cellular biology 122 9819431
2000 Opposing roles of pRB and p107 in adipocyte differentiation. Proceedings of the National Academy of Sciences of the United States of America 119 10995476
1995 Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins. Molecular and cellular biology 117 7791762
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
1993 A genetic analysis of the E2F1 gene distinguishes regulation by Rb, p107, and adenovirus E4. Molecular and cellular biology 115 8413230
1993 Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1. Journal of virology 113 8230483
1996 Human papillomavirus E7 oncoproteins bind a single form of cyclin E in a complex with cdk2 and p107. Virology 112 8553588
1993 Transcriptional repression by the Rb-related protein p107. Molecular biology of the cell 112 7685208
1996 The human cytomegalovirus IE1-72 protein interacts with the cellular p107 protein and relieves p107-mediated transcriptional repression of an E2F-responsive promoter. Journal of virology 103 8892909
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 102 9199292
1996 Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases. Proceedings of the National Academy of Sciences of the United States of America 100 8643455
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
2008 An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex. Molecular biology of the cell 95 18799622
1999 C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice. Molecular and cellular biology 94 10082561
1986 Purification, characterization, and structural properties of a single protein from rat basophilic leukemia (RBL-1) cells possessing 5-lipoxygenase and leukotriene A4 synthetase activities. Molecular pharmacology 94 3785138
1995 Association of p107 with Sp1: genetically separable regions of p107 are involved in regulation of E2F- and Sp1-dependent transcription. Molecular and cellular biology 93 7565695
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
1995 MDM2 transformation in the absence of p53 and abrogation of the p107 G1 cell-cycle arrest. Oncogene 90 8570197
1996 Simian virus 40 large T antigen alters the phosphorylation state of the RB-related proteins p130 and p107. Journal of virology 89 8627752
1999 Functional interaction between a novel protein phosphatase 2A regulatory subunit, PR59, and the retinoblastoma-related p107 protein. Oncogene 86 9927208
2005 p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2. Journal of cell science 83 15827088
1997 Differential expression of Rb2/p130 and p107 in normal human tissues and in primary lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 80 9815552
1995 Expression and activity of the retinoblastoma protein (pRB)-family proteins, p107 and p130, during L6 myoblast differentiation. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 80 8845306
2004 p107 regulates neural precursor cells in the mammalian brain. The Journal of cell biology 76 15353549
1996 Differential expression of the retinoblastoma gene family members pRb/p105, p107, and pRb2/p130 in lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 76 9816293
2002 Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4. Molecular and cellular biology 75 11884610
1994 Evidence for a protein domain superfamily shared by the cyclins, TFIIB and RB/p107. Nucleic acids research 73 8152925
1988 Staurosporine inhibits protein kinase C and prevents phorbol ester-mediated leukotriene D4 receptor desensitization in RBL-1 cells. Molecular pharmacology 73 2835653
1998 Distinct mechanisms control the accumulation of the Rb-related p107 and p130 proteins during cell growth. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 72 9563849
1998 p130 is dispensable in peripheral T lymphocytes: evidence for functional compensation by p107 and pRB. Molecular and cellular biology 70 9418868
2002 Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4. The Journal of biological chemistry 67 12006580
1993 Temporal regulation of cyclin A-p107 and p33cdk2 complexes binding to a human thymidine kinase promoter element important for G1-S phase transcriptional regulation. Proceedings of the National Academy of Sciences of the United States of America 67 8475104
1998 Dual cyclin-binding domains are required for p107 to function as a kinase inhibitor. Molecular and cellular biology 65 9710622
2019 RB, p130 and p107 differentially repress G1/S and G2/M genes after p53 activation. Nucleic acids research 64 31667499
2003 Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107. Proceedings of the National Academy of Sciences of the United States of America 62 14671316
2002 Expression of cell-cycle-regulated proteins pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) in prostatic gland adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 62 12060621
2002 p107 and p130 Coordinately regulate proliferation, Cbfa1 expression, and hypertrophic differentiation during endochondral bone development. Developmental biology 59 12086466
2008 Retinoblastoma protein (pRb), but not p107 or p130, is required for maintenance of enterocyte quiescence and differentiation in small intestine. The Journal of biological chemistry 58 18981186
1995 The interactions of E2F with pRB and with p107 are regulated via the phosphorylation of pRB and p107 by a cyclin-dependent kinase. Oncogene 56 7753545
1995 Viral oncoprotein binding to pRB, p107, p130, and p300. Virus research 56 7762286
1995 The Rb-related p107 protein can suppress E2F function independently of binding to cyclin A/cdk2. Molecular and cellular biology 55 7799940
2016 CRISPR/Cas9 mediated knockout of rb1 and rbl1 leads to rapid and penetrant retinoblastoma development in Xenopus tropicalis. Scientific reports 54 27739525
1999 RNA polymerase III transcription factor IIIB is a target for repression by pocket proteins p107 and p130. Molecular and cellular biology 54 10330166
2003 Rb and p107 are required for normal cerebellar development and granule cell survival but not for Purkinje cell persistence. Development (Cambridge, England) 53 12810584
2006 Phosphatidylinositol 3-kinase/protein kinase Czeta-induced phosphorylation of Sp1 and p107 repressor release have a critical role in histone deacetylase inhibitor-mediated derepression [corrected] of transcription of the luteinizing hormone receptor gene. Molecular and cellular biology 52 16943418
1996 Transcriptional repression and growth suppression by the p107 pocket protein. Molecular and cellular biology 52 8668177
2002 FGF signaling targets the pRb-related p107 and p130 proteins to induce chondrocyte growth arrest. The Journal of cell biology 51 12177046
1996 B-myb promotes S phase and is a downstream target of the negative regulator p107 in human cells. The Journal of biological chemistry 51 8621601
2003 Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Development (Cambridge, England) 50 12702649
2000 Disruption of the actin cytoskeleton leads to inhibition of mitogen-induced cyclin E expression, Cdk2 phosphorylation, and nuclear accumulation of the retinoblastoma protein-related p107 protein. Experimental cell research 50 10942577
2004 A dynamic equilibrium between CDKs and PP2A modulates phosphorylation of pRB, p107 and p130. Cell cycle (Georgetown, Tex.) 49 15467457
1994 pRB, p107 and the regulation of the E2F transcription factor. Journal of cell science. Supplement 49 7883798
1998 p130, p107, and pRb are differentially regulated in proliferating cells and during cell cycle arrest by alpha-interferon. The Journal of biological chemistry 47 9726970
1994 Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein. Molecular and cellular biology 47 7935440
1999 E2F/p107 and E2F/p130 complexes are regulated by C/EBPalpha in 3T3-L1 adipocytes. Nucleic acids research 45 10446255
2010 p107 in the public eye: an Rb understudy and more. Cell division 44 20359370
1985 Alterations in chromatin conformation are accompanied by reorganization of nonchromatin domains that contain U-snRNP protein p28 and nuclear protein p107. The Journal of cell biology 44 2991302
2006 JC virus T'135, T'136 and T'165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential. Journal of neurovirology 40 17162659
2002 The cancer preventive flavonoid silibinin causes hypophosphorylation of Rb/p107 and Rb2/p130 via modulation of cell cycle regulators in human prostate carcinoma DU145 cells. Cell cycle (Georgetown, Tex.) 39 12429923
1999 Rapid dephosphorylation of p107 following UV irradiation. Oncogene 39 9989818
1999 Domain mapping of the human cytomegalovirus IE1-72 and cellular p107 protein-protein interaction and the possible functional consequences. The Journal of general virology 38 10355776
1986 Macromolecular domains containing nuclear protein p107 and U-snRNP protein p28: further evidence for an in situ nuclear matrix. Molecular and cellular biochemistry 38 2941679
2005 p107 inhibits G1 to S phase progression by down-regulating expression of the F-box protein Skp2. The Journal of cell biology 37 15631990
2013 Proto-oncogene activity of melanoma antigen-A11 (MAGE-A11) regulates retinoblastoma-related p107 and E2F1 proteins. The Journal of biological chemistry 36 23853093
2007 The Retinoblastoma family member p107 regulates the rate of progenitor commitment to a neuronal fate. The Journal of cell biology 36 17591923
1995 In-vivo analysis of hpv e7 protein association with prb, p107 and p130. International journal of oncology 35 21556519

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