Affinage

Showing MYBL2 — B-MYB is a alias.

MYBL2

Myb-related protein B · UniProt P10244

Length
700 aa
Mass
78.8 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYBL2 (B-Myb) is a cell cycle-regulated transcription factor of the MYB family that governs the G1/S and G2/M gene-expression programs and is essential for proliferation, genome stability, and early development (PMID:3060855, PMID:1501895, PMID:10497154). Its transcription is repressed in G0/early G1 by an E2F-binding site cooperating with a contiguous CHR corepressor element and p107-containing E2F complexes, and is induced at the G1/S boundary (PMID:7642110, PMID:8760872, PMID:8621601). The latent activity of full-length B-Myb is held in check by an inhibitory C-terminal domain, which is relieved by cyclin A/E–Cdk2 phosphorylation at multiple Ser/Thr-Pro sites; this activation is amplified by Pin1-dependent prolyl isomerization that licenses further Cdk and Plk1 phosphorylation, and by phosphorylation-dependent acetylation by p300 (PMID:9094315, PMID:10593981, PMID:30321399, PMID:14973551). Activated B-Myb assembles with MuvB to form the MMB complex that drives late cell-cycle gene expression, and acts as a pioneer factor enabling FoxM1 to bind G2/M promoters; its overexpression disrupts the repressive DREAM complex through the LIN52 adapter (PMID:22513242, PMID:30206359). Beyond transcription, B-Myb forms a non-transcriptional complex with clathrin and filamin required for mitotic spindle stability, and B-Myb loss in model systems produces spindle/centrosome defects, reduced cyclin B1, polyploidy, and genome instability (PMID:18548008, PMID:16150706, PMID:18575582). B-Myb safeguards replication by activating ATM to restrain origin firing and limit replication stress in embryonic stem cells, and supports double-strand break repair in hematopoietic stem cells, where it is required to maintain the HSC pool (PMID:33779025, PMID:20715180, PMID:30082276, PMID:24516162). Its abundance is restrained by Cdc34–SCF(Skp2)-mediated degradation, by cyclin F binding that blocks Cdk-mediated activation to enforce G2 checkpoint maintenance, and by miR-29/miR-30 targeting of its 3'UTR during senescence (PMID:10871850, PMID:25557911, PMID:21187425). B-Myb knockout is embryonic lethal at E4.5–E6.5 with failure of inner cell mass formation (PMID:10497154).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1988 Medium

    Establishing that MYBL2 is a structural member of the MYB transcription factor family defined its candidate molecular identity as a DNA-binding regulator.

    Evidence cDNA cloning and sequence analysis revealing three conserved c-Myb-homologous DNA-binding domains

    PMID:3060855

    Open questions at the time
    • Sequence homology alone did not establish DNA-binding specificity or target genes
    • No functional or cell-cycle context
  2. 1992 High

    Linking B-myb expression to the cell cycle placed the gene in the G1/S transition rather than treating it as a constitutive factor.

    Evidence Northern blot of serum-stimulated synchronized 3T3 fibroblasts

    PMID:1501895

    Open questions at the time
    • mRNA timing did not reveal the protein-level regulatory mechanism
    • Did not identify upstream regulators of the promoter
  3. 1993 High

    Showing full-length B-Myb is intrinsically DNA-binding-incompetent unless its C-terminus is removed revealed an autoinhibitory architecture distinct from c-Myb.

    Evidence In vitro transcription/translation, gel-shift, GAL4 fusion and co-transfection reporter assays

    PMID:8382794

    Open questions at the time
    • Did not identify the physiological signal that relieves C-terminal inhibition
    • Endogenous target promoters remained undefined
  4. 1994 High

    Defining E2F/p107-dependent repression of the B-myb promoter, and its deregulation by HPV16 E7, explained how the gene is restricted to S phase and how it is hijacked in transformation.

    Evidence Reporter assays, E2F binding analysis, E7 mutant and promoter mutagenesis; p53/cyclin-Cdk2 bypass assays

    PMID:7937841 PMID:8112300

    Open questions at the time
    • The corepressor element cooperating with E2F was not yet defined
    • Mechanism by which B-Myb bypasses p53 arrest unresolved
  5. 1996 High

    Resolving the cooperating CHR corepressor element and DP-1/E2F heterodimers clarified the combinatorial logic of G0 promoter repression.

    Evidence Gel-shift with fractionated extract, promoter mutagenesis, in vivo footprinting; p107 reporter and BrdU assays

    PMID:8621601 PMID:8760872

    Open questions at the time
    • Did not address post-translational control of B-Myb protein activity
    • p107 down-modulation mechanism only partly defined
  6. 1999 High

    Comprehensive mapping of cyclin A/E–Cdk2 phosphorylation sites established the post-translational switch that converts repressed B-Myb into an active transactivator.

    Evidence Phosphopeptide radiosequencing, cell-free kinase assays, site mutagenesis and reporter assays (building on 1997 kinase studies)

    PMID:10593981 PMID:9012818 PMID:9094315

    Open questions at the time
    • The downstream consequences (acetylation, complex assembly) were not yet integrated
    • Did not define endogenous late cell-cycle target genes
  7. 1999 High

    Genetic knockout in mice defined B-Myb as essential for early embryogenesis and inner cell mass formation, establishing a non-redundant biological requirement.

    Evidence Gene-targeted knockout mice and in vitro blastocyst culture

    PMID:10497154

    Open questions at the time
    • Early lethality precluded analysis of later tissue roles
    • Molecular cause of ICM failure undefined at the time
  8. 2001 Medium

    Identifying SCF(Skp2)-mediated degradation and phosphorylation-dependent p300 acetylation showed that B-Myb activity is coupled to coordinated turnover and coactivator recruitment.

    Evidence Ubiquitination and co-IP assays with Cdc34/Skp2; in vivo acetylation and dominant-negative reporter assays

    PMID:10871850 PMID:11733503 PMID:14973551

    Open questions at the time
    • Single-lab biochemistry without structural confirmation of modification sites
    • Quantitative contribution of degradation vs activation to phenotype unclear
  9. 2005 High

    Loss-of-function in zebrafish tied B-Myb to mitotic spindle formation and cyclin B1 levels, extending its role from S-phase entry to mitotic fidelity and genome stability.

    Evidence Forward genetic crash&burn mutant, spindle imaging, and chemical suppressor screen with ATR knockdown epistasis

    PMID:16150706 PMID:16372403

    Open questions at the time
    • Whether spindle effects are transcriptional or direct was unresolved here
    • Mammalian relevance not yet established in this work
  10. 2008 High

    Discovery of the B-Myb–clathrin–filamin (Clafi) complex revealed a non-transcriptional function directly supporting mitotic spindle stability.

    Evidence Biochemical complex purification, co-IP, and mitotic spindle localization imaging; ESC knockdown spindle/centrosome analysis

    PMID:18548008 PMID:18575582

    Open questions at the time
    • How transcriptional and structural roles are partitioned in the cell is unclear
    • Regulation of Clafi complex assembly undefined
  11. 2009 High

    Defining B-Myb dissociation from the LINC/DREAM complex upon DNA damage, and its persistence in p53-mutant cells, connected B-Myb to G2 checkpoint control and recovery.

    Evidence Co-IP of LINC components, microarray, siRNA, and G2 checkpoint recovery assays in p53+/- backgrounds

    PMID:19383908 PMID:21480327

    Open questions at the time
    • Direct signal triggering dissociation only partly defined
    • Did not resolve MuvB/DREAM exchange mechanism at the molecular level
  12. 2010 High

    Conditional ESC studies and senescence miRNA work established that B-Myb safeguards the replication program and is silenced via the Rb pathway during senescence.

    Evidence Conditional knockout with DNA fiber analysis; miR-29/30 3'UTR reporter and compensatory-mutation rescue; p16 promoter ChIP

    PMID:20715180 PMID:20734103 PMID:21187425

    Open questions at the time
    • Direct vs indirect contribution of c-Myc/FoxM1 misregulation to fork defects not fully separated
    • p16 repression mechanism single-lab
  13. 2012 High

    Demonstrating B-Myb acts as a pioneer factor enabling FoxM1 promoter binding clarified the mechanistic hierarchy driving G2/M gene expression.

    Evidence Conditional knockout 3T3 cells, ChIP, and Myb-binding-site promoter mutagenesis on Birc5

    PMID:22513242

    Open questions at the time
    • Generality of pioneer behavior across all G2/M promoters not established
    • Chromatin-opening mechanism not directly resolved
  14. 2015 High

    Identifying cyclin F as a B-Myb suppressor that blocks cyclin A-mediated phosphorylation revealed a brake enforcing G2 checkpoint maintenance.

    Evidence RNAi screen, co-IP, phosphorylation assays, and G2 checkpoint assays after ionizing radiation

    PMID:25557911

    Open questions at the time
    • Stoichiometry and turnover of cyclin F–B-Myb interplay not quantified
    • Single-lab functional checkpoint data
  15. 2018 High

    Showing B-Myb overexpression disrupts DREAM via the MuvB/LIN52 adapter linked its abundance to the switch between repressive and activating MuvB complexes.

    Evidence Co-IP of DREAM/MMB components, MuvB-binding-domain mutants, and LIN52 S28 phosphorylation analysis

    PMID:30206359

    Open questions at the time
    • In vivo significance of DREAM disruption by overexpression not addressed
    • How physiological B-Myb levels balance the complexes unclear
  16. 2019 High

    Defining a Pin1-licensed stepwise Cdk-then-Plk1 phosphorylation cascade explained how B-Myb is progressively activated to drive late cell-cycle genes.

    Evidence Phosphorylation mapping, Pin1 binding, Plk1 docking assays, mutagenesis and reporter assays; UHMK1 BioID nuclear-enrichment study

    PMID:30321399 PMID:30936457

    Open questions at the time
    • Structural basis of ordered modification not resolved
    • UHMK1 contribution is single-lab and Medium confidence
  17. 2021 High

    ESC studies established that B-Myb activates ATM to restrain origin firing and limit replication stress, providing a mechanistic basis for its genome-stability role.

    Evidence Conditional knockout/knockdown, DNA fiber assays, ATM/Mre11 inhibition, and CDC7-inhibitor rescue of replication stress

    PMID:33779025

    Open questions at the time
    • Whether ATM activation is transcriptional or direct not fully resolved
    • Generality beyond ESCs not established here
  18. 2018 Medium

    Haploinsufficiency studies extended the genome-stability role to hematopoietic stem cells, linking reduced B-Myb to impaired DSB repair and telomere fragility.

    Evidence Mybl2 haploinsufficient mice, γH2AX kinetics, phospho-KAP1 analysis, and telomere FISH

    PMID:24516162 PMID:30082276

    Open questions at the time
    • Single-lab mechanistic readouts
    • Direct vs indirect effect on ATM substrate phosphorylation not separated
  19. 2023 Medium

    Cancer-context studies tied phosphorylation-activated MYBL2 to oncogenic transcriptional programs across multiple tumor types via direct promoter binding.

    Evidence ChIP, reporter assays, co-IP, and in vivo models linking MYBL2 to CDCA3/Wnt, RRM2, YAP1/Hippo, CCL2/TAM, APOBEC3B, and E2F2 loops

    PMID:28276478 PMID:33897882 PMID:34234118 PMID:34316028 PMID:36071275 PMID:37865750

    Open questions at the time
    • Each target axis rests on single-lab evidence
    • Direct vs network-level effects on these targets not always distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the structural (clathrin/filamin spindle) and transcriptional (MMB/FoxM1) functions of B-Myb are coordinated within a single cell cycle, and the structural basis of the ordered Cdk/Pin1/Plk1 activation switch, remain unresolved.
  • No high-resolution structure of B-Myb bound to MuvB or its phospho-regulatory domain
  • Quantitative interplay between degradation, cyclin F inhibition, and activation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0140110 transcription regulator activity 4 GO:0140104 molecular carrier activity 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-69306 DNA Replication 2 R-HSA-73894 DNA Repair 2
Partners
CYCLIN F (CCNF)FOXM1LIN52LIN9P107 (RBL1)P300 (EP300)PIN1SKP2
Complex memberships
B-Myb–clathrin–filamin (Clafi)DREAMLINCMMB (Myb-MuvB)

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 MYBL2 (B-Myb) encodes a protein of ~700 amino acids with three conserved domains homologous to the c-Myb DNA-binding domain, establishing it as a member of the MYB transcription factor family. cDNA cloning and sequence analysis Nucleic acids research Medium 3060855
1992 B-myb mRNA expression is cell cycle-regulated, induced in late G1 upon serum stimulation of quiescent fibroblasts and persisting through S phase, consistent with a role in G1/S transition. Northern blot of synchronized cells, serum stimulation of quiescent 3T3 fibroblasts Oncogene High 1501895
1993 Full-length B-Myb does not bind the c-Myb DNA-binding site (MBS-1) and cannot transactivate c-Myb target promoters; however, truncation of the B-Myb C-terminus releases latent DNA-binding competence, and B-Myb inhibits c-Myb transactivation in co-transfection assays. B-Myb and c-Myb can both weakly transactivate the DNA polymerase alpha promoter. In vitro transcription/translation, gel-shift assays, co-transfection reporter assays, GAL4 fusion assays Nucleic acids research High 8382794
1994 HPV16 E7 oncoprotein deregulates B-myb transcription by interacting with p107 at the E2F binding site of the B-myb promoter, causing both inappropriate G1 transcription and constitutive over-expression; regulation correlates with p107-containing E2F complexes rather than pRb. Reporter assays, E2F binding analysis, E7 mutant analysis, promoter mutagenesis The EMBO journal High 8112300
1994 Constitutive B-Myb expression can bypass p53-induced G1 arrest even in the presence of Waf1/Cip1 upregulation and cyclin E/Cdk2 inhibition; the DNA-binding domain of B-Myb is required for this activity. Ectopic expression rescue assays, co-transfection with p53 and B-Myb deletion mutants, cell cycle analysis Proceedings of the National Academy of Sciences of the United States of America High 7937841
1995 The human B-myb promoter is repressed in G0 by an E2F-binding site; mutation of this site increases reporter activity in quiescent cells. De-repression in S phase correlates with disappearance of a G0-specific E2F complex and appearance of a p107-containing complex. Luciferase reporter assays with promoter mutations, E2F binding analysis, cell cycle synchronization Gene High 7642110
1996 E2F-mediated repression of the B-myb promoter in G0/early G1 requires cooperation with a contiguous CHR (cell cycle homology region) corepressor element; DP-1 heterodimerizes with E2F-1, E2F-3, or E2F-4 to recognize the repressor element. Gel-shift assays with fractionated nuclear extract, promoter mutagenesis, in vivo footprinting Nucleic acids research High 8760872
1996 B-Myb overexpression induces DNA synthesis in p107-arrested Saos-2 cells; p107 down-modulates B-myb promoter activity and decreases E2F-mediated transactivation of the B-myb promoter. Transient transfection reporter assays, BrdU/DNA synthesis assays in p107-growth-arrested cells The Journal of biological chemistry Medium 8621601
1997 Cyclin A/Cdk2 phosphorylates B-Myb at its carboxy-terminal region, relieving repression by this domain and markedly stimulating its transcriptional transactivation function; endogenous B-Myb is phosphorylated during S phase. Tryptic phosphopeptide mapping, co-expression assays, transactivation reporter assays, cyclin A/Cdk2 baculovirus-expressed kinase assay Current biology : CB High 9094315
1997 Cyclin A or cyclin E co-expression activates B-MYB transcriptional activity and promotes S phase entry in Saos-2 cells; cyclin-dependent activation is demonstrated in an in vitro transcription assay and is specific to B-MYB (not c-MYB). Transfection/S phase entry assays, in vitro transcription assay, reporter assays Proceedings of the National Academy of Sciences of the United States of America High 9012818
1997 Cyclin A-mediated phosphorylation of B-Myb enhances its transactivation function; protein truncation just downstream of the evolutionarily conserved C-terminal domain also hyperactivates B-Myb, and these effects are partially additive. B-Myb synergizes with cyclin A to promote S phase entry. Reporter assays, co-expression with cyclin A/Cdk2, B-Myb truncation mutants, cell cycle analysis Oncogene Medium 9188859
1997 Cyclin A and cyclin E activate the trans-activating function of B-Myb by overcoming inhibition mediated by its carboxy-terminus; a conserved activation domain within B-Myb was localized by mutational analysis in yeast. Yeast transactivation assay, mutational analysis, co-expression in vertebrate cells Journal of molecular medicine (Berlin, Germany) Medium 9428611
1999 B-myb-deficient mice die at embryonic day E4.5–E6.5; in vitro blastocyst culture shows B-Myb is required for inner cell mass (ICM) formation. Only B-Myb among Myb family members is expressed in embryonic stem cells. Gene targeting knockout mice, in vitro blastocyst culture, expression analysis The Journal of biological chemistry High 10497154
1999 B-MYB transactivates its own promoter through a 120 bp SP1-binding proximal element; B-MYB does not directly bind this element but cooperates with SP1 via SP1 domain A, acting as a coactivator of SP1. Reporter assays, gel-shift assays, SP1 co-transfection, SP1-GAL4 fusion analysis, promoter deletion mapping Oncogene Medium 10022815
1999 B-Myb is phosphorylated at 10 Ser/Thr-Pro sites by cyclin A-Cdk2 and cyclin E-Cdk2 both in vivo and in vitro; phosphorylation at Ser581 negatively regulates DNA binding, and mutagenesis of all 10 sites abrogates cyclin A-dependent transactivation enhancement. Automated peptide radiosequencing of tryptic phosphopeptides from 32P-labeled B-Myb, cell-free kinase assay, mutagenesis, reporter assays The Journal of biological chemistry High 10593981
2000 B-Myb is degraded via ubiquitin-mediated proteolysis through the Cdc34-SCF(p45Skp2) pathway; cyclin A facilitates multiple ubiquitination of B-Myb through its C-terminal domain; B-Myb physically and functionally interacts with Cdc34 and p45Skp2. Co-immunoprecipitation, ubiquitination assays, C-terminal deletion mutants, ectopic expression of Cdc34 and Skp2 Oncogene High 10871850
2001 B-Myb is acetylated by the co-activator p300; the bromo and histone acetyltransferase domains of p300 are sufficient for interaction and acetylation; phosphorylation is essential for full B-Myb activity, and a phosphorylation-deficient mutant acts as a dominant-negative. In vivo acetylation assay, co-immunoprecipitation, dominant-negative suppression, reporter assays with phosphorylation-deficient mutants The Journal of biological chemistry Medium 11733503
2001 B-Myb forms an in vivo complex with p107 (but not pRb or p130) and overcomes p107-mediated G1 arrest independently of its transactivation function; B-Myb also interacts with repressors BS69 and N-CoR via its C-terminus. Co-immunoprecipitation, cell proliferation assay, dominant-negative experiments, S phase induction assays Cancer letters Medium 11485831
2001 PARP co-activates B-MYB by inducing phosphorylation at cyclin/Cdk2 sites; a B-MYB mutant lacking all Cdk2 phosphorylation sites is refractory to PARP-induced phosphorylation and co-activation. Co-immunoprecipitation, phosphorylation-deficient mutant analysis, reporter assays, co-expression Oncogene Medium 11781832
2002 B-Myb binds to an N-terminal domain of p107 (overlapping the cyclin-binding domain) that is distinct from the C-terminal pocket domain used by E2F; B-Myb and cyclin A2 form mutually exclusive complexes with p107; B-Myb enhances cyclin E kinase activity. Co-immunoprecipitation, GST pulldown, cyclin kinase activity assays, co-transfection Oncogene Medium 12439743
2003 The zinc finger protein ZPR9 physically interacts with B-MYB (via all three B-MYB functional domains) both in vitro and in vivo, enhances B-MYB transcriptional activity in a dose-dependent manner, and promotes nuclear accumulation of both proteins. Yeast two-hybrid, co-immunoprecipitation, in vivo binding assay, reporter assays, confocal localization The Journal of biological chemistry Medium 12645566
2004 B-Myb-dependent transactivation is stimulated by the co-activator p300; interaction maps to the E1A-binding region of p300 and the transactivation domain of B-Myb; cyclin A-mediated phosphorylation of B-Myb stimulates its acetylation by p300, required for full transactivation; cyclin D1 inhibits B-Myb activity by interfering with B-Myb–p300 interaction. Co-immunoprecipitation, reporter assays, cyclin A/D1 co-expression, acetylation assays, domain mapping Oncogene Medium 14973551
2004 B-MYB binds to transcriptional regulatory elements of the stress-related gene ApoJ/clusterin in a temperature-dependent manner and activates its expression as a pro-survival response to thermal stress; suppression of B-MYB transactivation by a dominant-negative only induces cell death when cells are exposed to high temperature. RNA interference, dominant-negative B-MYB, chromatin immunoprecipitation, cell death assays, temperature-shift experiments The Journal of biological chemistry Medium 15618219
2005 Loss-of-function mutation of bmyb in zebrafish (crash&burn mutant) causes defects in mitotic progression and spindle formation, decreased cyclin B1 levels, and genome instability; regulation of cyclin B levels by Bmyb appears to be the mechanism of mitotic accumulation. Zebrafish forward genetic screen, loss-of-function mutant analysis, cell cycle and spindle imaging, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 16150706
2005 Chemical suppressor screening in zebrafish bmyb mutants identified that S-phase delay (via ATR-dependent checkpoint) upregulates cyclin B1 mRNA and suppresses bmyb-dependent mitotic defects; ATR knockdown abrogates this suppression, placing bmyb upstream of cyclin B1 and the ATR checkpoint pathway. Small molecule suppressor screen in zebrafish embryos, ATR morpholino knockdown, cyclin B1 expression analysis Nature chemical biology High 16372403
2006 Nuclear EGFR associates with E2F1 in an EGF-dependent manner and both bind the B-Myb promoter cooperatively; EGFR kinase activity is required; promoter mutagenesis shows both E2F and EGFR target sites are needed for EGF-induced B-Myb activation. Co-immunoprecipitation, chromatin immunoprecipitation, promoter mutagenesis, reporter assays, kinase inhibitor experiments Molecular carcinogenesis Medium 16299810
2008 B-Myb forms a complex with clathrin and filamin (Myb-Clafi complex) that is required for normal localization of clathrin to the mitotic spindle; loss of this complex disrupts spindle stability and contributes to genome instability. Biochemical purification of B-Myb complex, co-immunoprecipitation, mitotic spindle localization imaging, functional spindle assays The EMBO journal High 18548008
2008 B-MYB knockdown in murine embryonic stem cells causes delayed G2/M transit, mitotic spindle and centrosome defects, and polyploidy/aneuploidy; B-Myb overexpression modestly up-regulates pou5f1 (Oct4) gene promoter activity in vitro. shRNA knockdown, cell cycle analysis by flow cytometry, immunofluorescence of spindle/centrosome, luciferase reporter for pou5f1 promoter PloS one High 18575582
2009 DNA damage triggers p53-dependent binding of p130 and E2F4 to the LINC complex with concurrent dissociation of B-MYB from LINC; in p53-mutant cells, B-MYB fails to dissociate from LINC, maintains G2/M gene expression after damage, and is required for recovery from the G2 DNA damage checkpoint. Co-immunoprecipitation of LINC components, microarray expression analysis, B-MYB siRNA knockdown, G2 checkpoint recovery assays Cancer research High 19383908
2010 miR-29 and miR-30 families repress B-Myb expression during senescence by binding conserved sites in the B-Myb 3'UTR; this repression requires Rb pathway activation; compensatory mutations in both miRNA and 3'UTR restore repression, and miR-29/30 introduction inhibits DNA synthesis. Reporter assays with wild-type and mutant B-Myb 3'UTR, miRNA transfection, compensatory mutation rescue, cell cycle analysis Proceedings of the National Academy of Sciences of the United States of America High 21187425
2010 B-Myb ablation in mouse ESCs leads to stalling of replication forks, superactivation of replication factories, disorganization of the replication program, and increased double-strand breaks; these effects are partly due to aberrant transcriptional regulation of c-Myc and FoxM1. Conditional B-myb knockout in mES cells, single DNA fiber analysis, 3D imaging, gene expression analysis Stem cells (Dayton, Ohio) High 20715180
2010 B-MYB binds a MYB-binding site (MBS) in the p16(INK4α) promoter in vivo and represses p16 transcription; knockdown of B-MYB upregulates p16 expression and impairs replicative ability. ChIP, promoter reporter assays, siRNA knockdown, replicative senescence assays Cellular and molecular life sciences : CMLS Medium 20734103
2011 MYBL2-LIN9 complex (LINC) activation is crucial for HCC progression; LINC integrity contributes to survival of DNA-damaged p53-null cells; siRNA-mediated MYBL2/LINC silencing reduces proliferation and induces apoptosis; doxorubicin triggers LIN9 dissociation from MYBL2 in p53-positive but not p53-null cells. Co-immunoprecipitation, siRNA knockdown, cell proliferation and apoptosis assays, western blotting in p53+/+ and p53-/- cell lines Hepatology (Baltimore, Md.) Medium 21480327
2012 B-Myb acts as a pioneer factor required for FoxM1 binding to G2/M gene promoters; conditional B-myb knockout reduces FoxM1 promoter binding without affecting FoxM1 protein levels or nuclear localization; Myb binding site mutation on Birc5 promoter prevents FoxM1 binding and activation. Conditional B-myb knockout 3T3 cells (floxed alleles + Cre), chromatin immunoprecipitation, promoter-reporter assays with Myb binding site mutations, gene expression analysis Biochimica et biophysica acta High 22513242
2014 Conditional inactivation of B-myb in vivo depletes the hematopoietic stem cell (HSC) pool; HSCs accumulate in S and G2/M phases; the defect is bone-marrow autonomous and affects common myeloid progenitors with relative sparing of granulocyte-macrophage progenitors. Conditional knockout mice, flow cytometry, cell cycle analysis, bone marrow transplantation, microarray Proceedings of the National Academy of Sciences of the United States of America High 24516162
2015 Cyclin F interacts with B-Myb via its cyclin box domain and suppresses B-Myb-driven transcriptional activation of mitosis-promoting genes; cyclin F interaction specifically inhibits cyclin A-mediated phosphorylation of B-Myb, and cyclin F depletion causes failure to maintain G2 arrest after ionizing radiation. RNA interference screen, co-immunoprecipitation, G2 checkpoint assays, phosphorylation assays, gene expression analysis Nature communications High 25557911
2017 B-Myb (MYBL2) binds the APOBEC3B (A3B) promoter and transactivates it, causing C-to-T cytosine transitions; EGFR blockade with afatinib attenuates B-Myb–A3B signaling. ChIP for B-Myb at A3B promoter, reporter assays, mutation analysis in breast cancer cells, pharmacological inhibition Scientific reports Medium 28276478
2017 Akt/FoxM1 signaling upregulates MYBL2 expression in glioma; inactivation of Akt or siRNA-mediated FoxM1 knockdown reduces MYBL2 protein levels, placing MYBL2 as a downstream effector of the Akt/FoxM1 pathway. siRNA knockdown, Akt inhibitor treatment, western blotting, qRT-PCR, luciferase reporter, ChIP Journal of experimental & clinical cancer research : CR Medium 28784180
2018 Overexpression of B-Myb disrupts the DREAM complex in human cells in a manner dependent on the intact MuvB-binding domain; B-Myb regulates LIN52 protein expression via a mechanism requiring S28 phosphorylation in LIN52, a key adapter for both DREAM and MMB complex assembly. Co-immunoprecipitation of DREAM/MMB components, B-Myb overexpression, MuvB-binding domain mutants, LIN52 phosphorylation site analysis, western blotting Oncogene High 30206359
2018 MYBL2 haploinsufficiency in mouse HSCs leads to defects in DNA double-strand break repair kinetics after ionizing radiation, characterized by unsustained ATM substrate KAP1 phosphorylation and telomere fragility. Mybl2 haploinsufficient mice, γH2AX kinetics after IR, phospho-KAP1 analysis, telomere FISH Cancer research Medium 30082276
2019 UHMK1 kinase stimulates nuclear enrichment of MYBL2 and thereby supports expression of MYBL2-target cell cycle genes (CCNB1, CCNB2, KIF20A, MAD2L1); MYBL2 is identified as a direct UHMK1 interaction partner by BioID proximity labeling and mass spectrometry. BioID labeling, mass spectrometry, co-immunoprecipitation, subcellular fractionation, gene expression analysis, YAPS127A transgenic mice Oncogene Medium 30936457
2019 B-Myb activation involves a stepwise phosphorylation mechanism: initial Cdk-dependent phosphorylation enables Pin1 binding and prolyl cis/trans isomerization, which in turn enables further Cdk-site phosphorylation and Plk1 docking, followed by Plk1-mediated phosphorylation to activate transcription of late cell cycle genes. Phosphorylation mapping, Pin1 binding assays, Plk1 docking assays, mutational analysis, reporter assays for late cell cycle gene activation Nucleic acids research High 30321399
2021 MYBL2 promotes castration resistance in prostate cancer by promoting YAP1 transcriptional activity via modulation of RhoA GTPase activity and LATS1 kinase activity (Hippo pathway); this is demonstrated by subcellular fractionation, ChIP, reporter assays, and in vivo experiments. Subcellular fractionation, western blotting, ChIP, luciferase reporter assays, RhoA/LATS1 activity assays, in vivo xenograft Theranostics Medium 33897882
2021 MYBL2 activates transcription of CDCA3 by directly binding its promoter; MYBL2 interacts with FOXM1 to co-regulate CDCA3 transcription; the MYBL2/FOXM1/CDCA3 axis activates Wnt/β-catenin signaling in bladder cancer. ChIP, co-immunoprecipitation, reporter assays, siRNA knockdown, western blotting Oncogene Medium 36071275
2021 MYBL2 directly binds the RRM2 gene promoter and activates its transcription during S phase together with TAF15 and MuvB components; MYBL2 is essential for CRC cell DNA synthesis and cell cycle progression in an RRM2-dependent manner. ChIP, co-immunoprecipitation, reporter assays, siRNA/ectopic expression, DNA synthesis assays, xenograft Cell death & disease Medium 34234118
2021 MYBL2 activates ATM and suppresses replication stress in embryonic stem cells; loss of MYBL2 or ATM inhibition causes replication fork slowing, fork stalling, and elevated origin firing; CDC7 inhibition rescues this replication stress, implicating uncontrolled origin firing as the underlying mechanism. Conditional MYBL2 knockout/knockdown in ESCs, DNA fiber assays, ATM/Mre11 inhibitors, CDC7 inhibitor rescue, origin firing analysis EMBO reports High 33779025
2010 B-MYB interacts with STRAP and enhances STRAP-mediated inhibition of TGF-β signaling by modulating SMAD3/SMAD7-TGF-β receptor complex formation; B-MYB also stimulates STRAP-mediated p53-induced apoptosis; confocal microscopy showed B-MYB prevents SMAD3 nuclear translocation. Co-immunoprecipitation, confocal microscopy, reporter assays, co-expression experiments, domain mapping The Journal of biological chemistry Medium 21148321
2004 Cytosolic phospholipase A2 (cPLA2) physically interacts with B-Myb in both cytoplasm and nucleus, negatively regulating B-Myb-dependent c-Myc gene expression; a catalytically inactive cPLA2 mutant lacking B-Myb binding does not inhibit B-Myb-dependent c-myc expression. Co-immunoprecipitation, reporter assays, genetic knockout mice (cPLA2-/-), siRNA, mutant cPLA2 analysis The Journal of biological chemistry Medium 14769798
2021 B-Myb and E2F2 form physical complexes in colorectal cancer cells, mutually transactivate each other's promoters, and constitute reciprocal feed-forward transactivation loops; both are required for ERK and AKT signaling pathway activation. Co-immunoprecipitation, ChIP, reporter assays, siRNA knockdown, RNA-seq, in vivo orthotopic models Oncogene Medium 34316028
2023 MYBL2 transcriptionally activates CCL2 by binding its promoter, promoting TAM recruitment and M2-like polarization; CDK2 phosphorylates MYBL2 to promote its transcriptional function; CDK2 inhibition (CVT-313) reprograms the tumor microenvironment. ChIP, luciferase reporter assays, syngeneic mouse model, flow cytometry, qRT-PCR, ELISA Cancer cell international Medium 37865750

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis. Cell death & disease 256 28640249
1988 Isolation of human cDNA clones of myb-related genes, A-myb and B-myb. Nucleic acids research 247 3060855
2010 miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proceedings of the National Academy of Sciences of the United States of America 177 21187425
2006 Co-regulation of B-Myb expression by E2F1 and EGF receptor. Molecular carcinogenesis 153 16299810
2005 A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility. Proceedings of the National Academy of Sciences of the United States of America 142 16150706
2005 Small molecules that delay S phase suppress a zebrafish bmyb mutant. Nature chemical biology 140 16372403
1994 HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of p107/E2F complexes. The EMBO journal 132 8112300
1991 Expression of c-myb and B-myb, but not A-myb, correlates with proliferation in human hematopoietic cells. Blood 132 1984793
1999 B-myb is required for inner cell mass formation at an early stage of development. The Journal of biological chemistry 127 10497154
2005 B-MYB, a transcription factor implicated in regulating cell cycle, apoptosis and cancer. European journal of cancer (Oxford, England : 1990) 126 16198555
1994 Constitutive expression of B-myb can bypass p53-induced Waf1/Cip1-mediated G1 arrest. Proceedings of the National Academy of Sciences of the United States of America 123 7937841
1992 B-myb antisense oligonucleotides inhibit proliferation of human hematopoietic cell lines. Blood 112 1586718
1999 B-myb promoter retargeting of herpes simplex virus gamma34.5 gene-mediated virulence toward tumor and cycling cells. Journal of virology 105 10438845
1997 Phosphorylation and activation of B-Myb by cyclin A-Cdk2. Current biology : CB 101 9094315
1997 Activation of human B-MYB by cyclins. Proceedings of the National Academy of Sciences of the United States of America 98 9012818
2003 Cell cycle regulation by the B-Myb transcription factor. Cellular and molecular life sciences : CMLS 96 14625684
2008 B-MYB is essential for normal cell cycle progression and chromosomal stability of embryonic stem cells. PloS one 88 18575582
2008 In vitro and in vivo analysis of B-Myb in basal-like breast cancer. Oncogene 88 19043454
2017 Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma. Journal of experimental & clinical cancer research : CR 87 28784180
1992 Characterization and cell cycle-regulated expression of mouse B-myb. Oncogene 85 1501895
1993 Transcription regulation by murine B-myb is distinct from that by c-myb. Nucleic acids research 81 8382794
2021 MYBL2 disrupts the Hippo-YAP pathway and confers castration resistance and metastatic potential in prostate cancer. Theranostics 80 33897882
1995 Cell-cycle regulation of human B-myb transcription. Gene 80 7642110
2012 Binding of FoxM1 to G2/M gene promoters is dependent upon B-Myb. Biochimica et biophysica acta 77 22513242
2009 B-MYB is required for recovery from the DNA damage-induced G2 checkpoint in p53 mutant cells. Cancer research 77 19383908
2000 Degradation of B-Myb by ubiquitin-mediated proteolysis: involvement of the Cdc34-SCF(p45Skp2) pathway. Oncogene 73 10871850
1997 B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein truncation. Oncogene 73 9188859
1991 Growth regulated expression of B-myb in fibroblasts and hematopoietic cells. Journal of cellular physiology 72 1717494
1996 Cell cycle-regulated repression of B-myb transcription: cooperation of an E2F site with a contiguous corepressor element. Nucleic acids research 70 8760872
2015 KDM4/JMJD2 Histone Demethylase Inhibitors Block Prostate Tumor Growth by Suppressing the Expression of AR and BMYB-Regulated Genes. Chemistry & biology 68 26364928
2017 MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma. Histopathology 66 28594149
2015 Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control. Nature communications 64 25557911
2014 Cellular senescence and aging: the role of B-MYB. Aging cell 64 24981831
1999 B-Myb protein in cellular proliferation, transcription control, and cancer: latest developments. Journal of cellular physiology 64 10228942
2019 YAP-dependent induction of UHMK1 supports nuclear enrichment of the oncogene MYBL2 and proliferation in liver cancer cells. Oncogene 57 30936457
2011 Activation of v-Myb avian myeloblastosis viral oncogene homolog-like2 (MYBL2)-LIN9 complex contributes to human hepatocarcinogenesis and identifies a subset of hepatocellular carcinoma with mutant p53. Hepatology (Baltimore, Md.) 55 21480327
2018 The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb. Oncogene 54 30206359
2018 Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis. Cell death & disease 53 30305611
2017 MYBL2 Is Targeted by miR-143-3p and Regulates Breast Cancer Cell Proliferation and Apoptosis. Oncology research 53 29268817
2024 Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer. Frontiers in immunology 51 39136009
2020 MYBL2 amplification in breast cancer: Molecular mechanisms and therapeutic potential. Biochimica et biophysica acta. Reviews on cancer 51 32853735
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
2010 B-Myb is critical for proper DNA duplication during an unperturbed S phase in mouse embryonic stem cells. Stem cells (Dayton, Ohio) 49 20715180
2008 A B-Myb complex containing clathrin and filamin is required for mitotic spindle function. The EMBO journal 49 18548008
2001 Effects of B-Myb on gene transcription: phosphorylation-dependent activity ans acetylation by p300. The Journal of biological chemistry 49 11733503
2017 B-Myb Is Up-Regulated and Promotes Cell Growth and Motility in Non-Small Cell Lung Cancer. International journal of molecular sciences 48 28555007
2011 B-Myb, cancer, senescence, and microRNAs. Cancer research 47 21828240
2010 Mybl2 expression is under genetic control and contributes to determine a hepatocellular carcinoma susceptible phenotype. Journal of hepatology 47 21419759
2001 B-myb rescues ras-induced premature senescence, which requires its transactivation domain. Cancer letters 46 11485831
2022 MYBL2 promotes proliferation and metastasis of bladder cancer through transactivation of CDCA3. Oncogene 45 36071275
1999 Phosphorylation of B-Myb regulates its transactivation potential and DNA binding. The Journal of biological chemistry 45 10593981
2020 Overexpression of MYBL2 promotes proliferation and migration of non-small-cell lung cancer via upregulating NCAPH. Molecular and cellular biochemistry 43 32200471
2014 B-myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development. Proceedings of the National Academy of Sciences of the United States of America 43 24516162
2015 ATAD2 overexpression links to enrichment of B-MYB-translational signatures and development of aggressive endometrial carcinoma. Oncotarget 41 26308378
1999 B-MYB transactivates its own promoter through SP1-binding sites. Oncogene 41 10022815
2021 A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer. Cell death & disease 36 34234118
2003 Enhancement of B-MYB transcriptional activity by ZPR9, a novel zinc finger protein. The Journal of biological chemistry 36 12645566
2021 CDCA8, targeted by MYBL2, promotes malignant progression and olaparib insensitivity in ovarian cancer. American journal of cancer research 34 33575078
1997 B-Myb, a repressed trans-activating protein. Journal of molecular medicine (Berlin, Germany) 34 9428611
2018 B-Myb Mediates Proliferation and Migration of Non-Small-Cell Lung Cancer via Suppressing IGFBP3. International journal of molecular sciences 33 29772705
2013 MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy. eLife 33 23878725
2019 LncRNA LOXL1-AS1 regulates the tumorigenesis and development of lung adenocarcinoma through sponging miR-423-5p and targeting MYBL2. Cancer medicine 31 31758653
2014 B-Myb regulates snail expression to promote epithelial-to-mesenchymal transition and invasion of breast cancer cell. Medical oncology (Northwood, London, England) 30 25502082
2021 B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2. Oncogene 29 34316028
2020 circRNA circ-MYBL2 is a novel tumor suppressor and potential biomarker in multiple myeloma. Human cell 29 33058028
2019 Activation of the oncogenic transcription factor B-Myb via multisite phosphorylation and prolyl cis/trans isomerization. Nucleic acids research 28 30321399
2010 B-MYB delays cell aging by repressing p16 (INK4α) transcription. Cellular and molecular life sciences : CMLS 28 20734103
2004 Temperature-dependent modification and activation of B-MYB: implications for cell survival. The Journal of biological chemistry 28 15618219
2017 B-Myb Induces APOBEC3B Expression Leading to Somatic Mutation in Multiple Cancers. Scientific reports 27 28276478
2011 MYBL2, a link between proliferation and differentiation in maturing colon epithelial cells. Journal of cellular physiology 27 20857481
2004 The cooperation of B-Myb with the coactivator p300 is orchestrated by cyclins A and D1. Oncogene 27 14973551
2022 E2F2 promotes lung adenocarcinoma progression through B-Myb- and FOXM1-facilitated core transcription regulatory circuitry. International journal of biological sciences 26 35844795
2016 Downregulation of B-myb promotes senescence via the ROS-mediated p53/p21 pathway, in vascular endothelial cells. Cell proliferation 26 27878894
2022 LncRNA-MALAT1 Regulates Cancer Glucose Metabolism in Prostate Cancer via MYBL2/mTOR Axis. Oxidative medicine and cellular longevity 25 35557985
2020 miR-30a inhibits androgen-independent growth of prostate cancer via targeting MYBL2, FOXD1, and SOX4. The Prostate 25 32294305
2019 Circ_0006332 promotes growth and progression of bladder cancer by modulating MYBL2 expression via miR-143. Aging 25 31756170
2018 MYBL2 Supports DNA Double Strand Break Repair in Hematopoietic Stem Cells. Cancer research 24 30082276
2001 Regulation of the cell cycle by B-Myb. Blood cells, molecules & diseases 24 11259164
2001 PARP co-activates B-MYB through enhanced phosphorylation at cyclin/cdk2 sites. Oncogene 23 11781832
2023 The MYBL2-CCL2 axis promotes tumor progression and resistance to anti-PD-1 therapy in ovarian cancer by inducing immunosuppressive macrophages. Cancer cell international 21 37865750
2021 MYBL2 and ATM suppress replication stress in pluripotent stem cells. EMBO reports 21 33779025
2002 B-Myb overcomes a p107-mediated cell proliferation block by interacting with an N-terminal domain of p107. Oncogene 21 12439743
2011 Mybl2, downregulated during colon epithelial cell maturation, is suppressed by miR-365. American journal of physiology. Gastrointestinal and liver physiology 20 21737779
2017 Antibiosis and bmyB Gene Presence As Prevalent Traits for the Selection of Efficient Bacillus Biocontrol Agents against Crown Gall Disease. Frontiers in plant science 19 28855909
1991 Chromosome locations of the MYB related genes, AMYB and BMYB. Cancer research 18 2065336
2003 Stimulation of the murine Uchl1 gene promoter by the B-Myb transcription factor. Lung cancer (Amsterdam, Netherlands) 17 14512183
1997 Redundant functions of B-Myb and c-Myb in differentiating myeloid cells. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 17 9419419
1996 Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q 13.1. Genomics 17 8812502
2023 Transcription factor B-MYB activates lncRNA CCAT1 and upregulates SOCS3 to promote chemoresistance in colorectal cancer. Chemico-biological interactions 16 36812959
2023 miR-200b/MYBL2/CDK1 suppresses proliferation and induces senescence through cell cycle arrest in ovine granulosa cells. Theriogenology 16 37257219
2022 Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) expression in glioblastoma is driven by ETS1- and MYBL2-dependent transcriptional activation. Cell death discovery 16 35228525
2021 MYBL2-Driven Transcriptional Programs Link Replication Stress and Error-prone DNA Repair With Genomic Instability in Lung Adenocarcinoma. Frontiers in oncology 16 33489883
2008 B-Myb regulates the A(2B) adenosine receptor in vascular smooth muscle cells. Journal of cellular biochemistry 16 17979185
2022 Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma. Frontiers in oncology 15 35664780
2022 A targetable MYBL2-ATAD2 axis governs cell proliferation in ovarian cancer. Cancer gene therapy 15 36151333
2014 B-myb is a gene implicated in cell cycle and proliferation of breast cancer. International journal of clinical and experimental pathology 15 25337223
2011 MYBL2 (B-MYB) in cervical cancer: putative biomarker. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 15 21270603
2004 B-Myb-dependent regulation of c-Myc expression by cytosolic phospholipase A2. The Journal of biological chemistry 15 14769798
2025 MYBL2 promotes cell proliferation and inhibits cell apoptosis via PI3K/AKT and BCL2/BAX/Cleaved-caspase-3 signaling pathway in gastric cancer cells. Scientific reports 14 40097530
2010 B-MYB positively regulates serine-threonine kinase receptor-associated protein (STRAP) activity through direct interaction. The Journal of biological chemistry 14 21148321

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