Affinage

MYB

Transcriptional activator Myb · UniProt P10242

Length
640 aa
Mass
72.3 kDa
Annotated
2026-06-10
100 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

c-Myb is a nuclear, nuclear-matrix-associated sequence-specific transcription factor that serves as a master regulator of definitive hematopoiesis: genetic ablation in mice abolishes adult-type fetal liver hematopoiesis while sparing primitive yolk-sac erythropoiesis (PMID:1709592, PMID:3014652), a requirement conserved to zebrafish where a DNA-recognition-helix mutation in repeat 3 selectively eliminates definitive blood (PMID:20823231). Its DNA-binding domain functions as a pioneer factor whose repeats bind histones and open chromatin, an activity destroyed by the D152V mutation in repeat 3 (PMID:28472346). Through direct binding to Myb sites, c-Myb activates a broad differentiation-associated target program including cdc2, c-myc, CD34, KLF1, LMO2, Bmi1, Gata3, Tcf7, and the miR-200 family, and represses Zeb2 and T-bet (PMID:8420994, PMID:8474446, PMID:7509358, PMID:20686118, PMID:21960247, PMID:17641686, PMID:30778251, PMID:24067373, PMID:28423310); it balances erythroid versus megakaryocytic fate (via KLF1/LMO2) and stage-specific lymphoid programs, and supports thymocyte survival by inducing Bcl-xL (PMID:20686118, PMID:20142358). c-Myb governs successive checkpoints across the immune system — early T-cell maturation, the pro-B to pre-B transition and B-lineage survival, RAG-2-dependent recombination, helper/cytotoxic T fate, CD8 memory, and CXCL12-dependent plasma cell homing to bone marrow (PMID:10323859, PMID:16169500, PMID:19843942, PMID:11781241, PMID:8551234, PMID:17641686, PMID:30778251, PMID:26077717) — and also controls colonic crypt progenitor proliferation and smooth-muscle differentiation, extending its role beyond blood (PMID:17360438, PMID:18187733). Transcriptional output is set by coactivator recruitment: CBP and p300 bind the transactivation/negative regulatory domain and acetylate defined C-terminal lysines to boost DNA binding and activity, with the p300-interacting M303V mutation deranging HSC homeostasis (PMID:8598284, PMID:10656693, PMID:11073948, PMID:15691758); c-Myb competes with GATA-1 for CBP and is antagonized by c-Maf and ZEB1 (PMID:10644988, PMID:9566892, PMID:24067373). c-Myb is integrated into chromatin machinery by joining the menin/MLL complex to promote H3K4 methylation at HOXA9 (PMID:20093773). Its abundance and activity are tuned by an intramolecular EVES-domain autoinhibition relieved by Pin1 and p100 (PMID:8756344, PMID:18359295, PMID:9809063), by phosphorylation (CKII at Ser-11/12 enhancing DNA binding, the Wnt-driven TAK1–HIPK2–NLK cascade and hyperphosphorylation driving proteasomal degradation) (PMID:7735324, PMID:7478531, PMID:15082531, PMID:10851088), and by TRAF7-stimulated sumoylation that sequesters it to the cytoplasm (PMID:16162816); oncogenic activation requires N- or C-terminal truncation that removes these autoinhibitory controls (PMID:2072904), and chaperone-disrupting drugs that destabilize c-Myb are anti-leukemic (PMID:29089643, PMID:35368048).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1986 Medium

    Establishing that the c-myb product is a nuclear, matrix-associated protein placed it in the compartment where it could act transcriptionally.

    Evidence Immunostaining and nuclear fractionation in leukemic cells

    PMID:3014652

    Open questions at the time
    • Did not define DNA-binding specificity or target genes
    • Nuclear matrix association not linked to function
  2. 1988 Medium

    Gain-of-function showed c-myb actively blocks differentiation, framing it as a differentiation-suppressing regulator rather than a passive marker.

    Evidence Constitutive c-myb expression in DMSO-treated Friend erythroleukemia cells

    PMID:2832742

    Open questions at the time
    • Mechanism of differentiation block not defined
    • Direct target genes not identified
  3. 1988 Medium

    Characterizing c-myb protein turnover as energy-dependent and ubiquitin-independent opened the question of how its abundance is controlled.

    Evidence Pulse-chase with lysosomal/energy/ubiquitin inhibitors and heat shock

    PMID:3043180

    Open questions at the time
    • Degradation pathway not molecularly identified
    • Later work implicated proteasome, partly contradicting ubiquitin-independence
  4. 1991 High

    Knockout and truncation analyses defined c-myb's essential physiological role in definitive hematopoiesis and revealed that its termini are autoinhibitory checkpoints whose removal causes transformation.

    Evidence Mouse c-myb knockout embryos; retroviral expression of truncated c-Myb in chicken bone marrow transformation assay

    PMID:1709592 PMID:2072904

    Open questions at the time
    • Direct hematopoietic target genes not yet mapped
    • Mechanism by which termini suppress transformation undefined
  5. 1993 Medium

    Identification of direct promoter targets (cdc2, c-myc, CD34) and CKII phosphorylation established c-Myb as a sequence-specific activator whose DNA binding is post-translationally tuned.

    Evidence Reporter assays with Myb-site mutagenesis, EMSA, in vitro CKII kinase assay

    PMID:7509358 PMID:7735324 PMID:8420994 PMID:8474446

    Open questions at the time
    • In vivo occupancy not demonstrated at this stage
    • Physiological kinases acting on Ser-11/12 in cells unclear
  6. 1996 High

    Discovery of CBP/p100 coactivation and the autoinhibitory EVES motif defined the dual control of c-Myb activity by coactivator recruitment and intramolecular folding, and showed combinatorial promoter activation with C/EBPalpha and PU.1.

    Evidence Yeast two-hybrid, GST pulldown, reporter and coactivation assays; cooperative neutrophil elastase promoter activation

    PMID:8598284 PMID:8756344 PMID:8756629

    Open questions at the time
    • How EVES autoinhibition is relieved physiologically not yet known
    • Synergistic DNA binding with C/EBPalpha/PU.1 not demonstrable in EMSA
  7. 1998 High

    Pim-1 phosphorylation of p100 and c-Maf antagonism linked c-Myb activity to upstream Ras signaling and to lineage-specific repression.

    Evidence Yeast two-hybrid, in vitro kinase, co-IP, reporter assays; c-Maf co-IP and CD13 promoter assays

    PMID:9566892 PMID:9809063

    Open questions at the time
    • Direct phosphorylation target on c-Myb itself not shown for Pim-1
    • Structural basis of Myb-Maf repression unresolved
  8. 1999 High

    Conditional and chimeric genetics pinpointed c-Myb as required at a specific early T-cell maturation checkpoint, refining its hematopoietic role to discrete developmental transitions.

    Evidence c-Myb-null/Rag1 chimeric mice with flow cytometric staging

    PMID:10323859

    Open questions at the time
    • Target genes controlling this transition not identified
    • Cell-intrinsic vs niche contribution not fully separated
  9. 2000 High

    Acetylation by p300/CBP at defined C-terminal lysines and competitive CBP sequestration by GATA-1 established acetylation and coactivator competition as quantitative tuners of c-Myb output, while phosphorylation-driven hyperphosphorylation linked activity to proteasomal turnover.

    Evidence In vitro/in vivo acetyltransferase assays with site mutants, EMSA, co-IP; okadaic acid and proteasome inhibitor pulse-chase

    PMID:10644988 PMID:10656693 PMID:10851088 PMID:11073948

    Open questions at the time
    • Identity of physiological degradation-triggering kinases not defined here
    • Crosstalk between acetylation and phosphorylation undefined
  10. 2002 High

    Crystallography of the c-Myb DBD with C/EBPbeta and cooperative binding with Pax-5 revealed long-range protein-protein interactions and DNA looping as a mechanism for combinatorial target activation.

    Evidence X-ray crystallography, GST pulldown, AFM; EMSA, co-IP and reporter assays at the RAG-2 promoter

    PMID:11781241 PMID:11792321

    Open questions at the time
    • In vivo prevalence of DNA looping unknown
    • Generalizability beyond these partners untested
  11. 2004 High

    The Wnt-1/TAK1–HIPK2–NLK cascade was defined as a signaling route that phosphorylates and degrades c-Myb to permit differentiation, connecting developmental signaling to c-Myb stability.

    Evidence Co-IP, in vitro kinase, ubiquitination and proteasome assays, M1 differentiation

    PMID:15082531

    Open questions at the time
    • Precise phosphodegron residues not fully mapped
    • E3 ligase mediating degradation not identified
  12. 2005 High

    A p300-interaction-disrupting point mutation (M303V) and TRAF7-driven sumoylation tied specific molecular interfaces to HSC homeostasis and to cytoplasmic sequestration, while B-cell genetics defined the pro-B to pre-B requirement.

    Evidence ENU M303V allele with HSC phenotyping; TRAF7 co-IP, sumoylation, fractionation; conditional B-cell Myb inactivation

    PMID:15691758 PMID:16162816 PMID:16169500

    Open questions at the time
    • How sumoylation and acetylation are coordinated unclear
    • Direct B-cell survival target genes not all identified
  13. 2007 High

    Direct activation of Gata3 in T cells, miR-150 targeting of c-Myb in B cells, and the colonic crypt requirement extended c-Myb's regulatory logic to lineage specification, post-transcriptional control, and non-hematopoietic progenitors.

    Evidence Conditional KO/transgenic mice, reporter assays; miR-150 gain/loss with c-Myb epistasis; hypomorphic alleles and colon deletion with Cyclin E1 readout

    PMID:17360438 PMID:17641686 PMID:17923094

    Open questions at the time
    • Full target networks downstream of Gata3/Cyclin E1 not mapped
    • miR-150 regulation in other lineages incompletely defined
  14. 2008 Medium

    Pin1 isomerization at the EVES motif, alternative C-terminal splicing, and the smooth-muscle differentiation requirement diversified the understanding of how c-Myb activity and specificity are generated.

    Evidence Co-IP/MS at S528 with reporter assays; RT-PCR and functional assays of splice variants; c-myb-/- ES cell SMC differentiation

    PMID:18187733 PMID:18195038 PMID:18359295

    Open questions at the time
    • Functional consequences of individual splice variants in vivo unclear
    • Pin1-EVES axis link to degradation not resolved
  15. 2010 High

    Integration into the menin/MLL complex and direct KLF1/LMO2 activation defined how c-Myb shapes chromatin state and erythroid-versus-megakaryocyte fate, while the zebrafish allele confirmed evolutionary conservation of its definitive-hematopoiesis role.

    Evidence Reciprocal co-IP, ChIP, knockdown with H3K4me readout; ChIP/reporter with KLF1/LMO2 rescue; zebrafish ENU missense allele; conditional thymocyte Bcl-xL rescue

    PMID:20093773 PMID:20142358 PMID:20686118 PMID:20823231

    Open questions at the time
    • Stoichiometry/architecture of c-Myb within the MLL complex undefined
    • Genome-wide co-occupancy with menin/MLL not fully mapped
  16. 2017 High

    Demonstration that the c-Myb DBD binds histones and opens chromatin defined it mechanistically as a pioneer factor, and chaperone-disrupting drugs revealed its therapeutic vulnerability in AML.

    Evidence ATAC-seq, histone binding, D152V mutagenesis in K562; mebendazole/HSP70 and miR-200 ChIP/reporter; T-bet repression in B cells

    PMID:24067373 PMID:28423310 PMID:28472346 PMID:29089643

    Open questions at the time
    • Genome-wide rules for pioneer-mode site selection incomplete
    • Whether chaperone-dependent stability is leukemia-selective unclear
  17. 2019 High

    Domain-resolved genetics in CD8 T cells separated c-Myb's transactivation function (restraining effector differentiation via Tcf7/Zeb2) from its negative regulatory domain's survival function, and earlier work tied it to plasma cell homing and B-lineage survival programs.

    Evidence Conditional KO, overexpression, domain mutants, adoptive transfer and infection; CXCL12 migration assay; Ebf1/CD127 rescue in pro-B cells

    PMID:19843942 PMID:26077717 PMID:30778251

    Open questions at the time
    • How the NRD promotes survival mechanistically undefined
    • Direct survival target genes downstream of the NRD unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the layered post-translational code (phosphorylation, acetylation, sumoylation, isomerization), EVES autoinhibition, and pioneer chromatin engagement are integrated in real time to select context-specific target programs across lineages remains unresolved.
  • No unified model linking modification state to genome-wide occupancy
  • E3 ligase(s) and full phosphodegron for proteasomal turnover unidentified
  • Quantitative contribution of splice variants to lineage-specific output unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 6 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 11 R-HSA-392499 Metabolism of proteins 7 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 2
Partners
CREBBPEP300GATA1MAFMEN1PAX5PIN1TRAF7
Complex memberships
menin/MLL histone methyltransferase complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 c-myb is required for definitive (adult-type) fetal liver hematopoiesis but not for primitive (yolk sac) erythropoiesis; homozygous c-myb knockout mice die by embryonic day 15 with severe anemia due to failure of adult-type hematopoietic progenitor cell proliferation in the fetal liver. Homologous recombination knockout in mouse embryonic stem cells; phenotypic analysis of homozygous mutant embryos Cell High 1709592
1988 Constitutive expression of full-length human c-myb cDNA blocks DMSO-induced erythroid differentiation of Friend murine erythroleukemia cells, establishing a causal role for c-myb in inhibiting erythroid differentiation. Stable transfection of c-myb expression construct into F-MEL cells; differentiation assay with DMSO; methotrexate amplification of transgene Molecular and cellular biology Medium 2832742
1996 CBP (CREB-binding protein) is a direct transcriptional coactivator of c-Myb; CBP binds the transactivation domain of c-Myb in a phosphorylation-independent manner in vitro, and a c-Myb/CBP complex forms in vivo (yeast two-hybrid). CBP stimulates c-Myb-dependent transcription, and adenovirus E1A (which binds CBP) inhibits c-Myb-induced transactivation. In vitro GST pulldown, yeast two-hybrid, transactivation reporter assays, antisense CBP inhibition, E1A competition assay Genes & development High 8598284
2005 c-Myb controls hematopoietic stem cell proliferation and differentiation through interaction with the transcriptional coactivator p300; a point mutation (M303V) in the c-Myb transactivation domain disrupts its interaction with p300, causing thrombocytosis, anemia, lymphopenia, absence of eosinophils, and a 10-fold increase in cycling HSCs. ENU mutagenesis screen; identification of M303V point mutation; co-immunoprecipitation of c-Myb/p300; transactivation assays; hematopoietic phenotyping; cell cycle analysis Developmental cell High 15691758
1998 Pim-1 kinase binds to p100 (a c-Myb transcriptional coactivator) via yeast two-hybrid, phosphorylates p100 in vitro, forms a stable complex with p100 in animal cells, and stimulates c-Myb transcriptional activity in a p100-dependent manner downstream of Ras signaling. Yeast two-hybrid screen; in vitro kinase assay; co-immunoprecipitation; transactivation reporter assays Molecular cell High 9809063
1996 The EVES motif in the c-Myb C-terminus mediates intramolecular interaction with the N-terminal DNA-binding domain (via yeast two-hybrid), and also interacts intermolecularly with p100 coactivator. The EVES motif contains a phosphorylation site implicated in negative regulation of c-Myb activity. Yeast two-hybrid assay; domain mapping; identification of EVES motif; functional coactivation assays Genes & development Medium 8756344
1996 c-Myb, C/EBPalpha, and PU.1 cooperate to activate the neutrophil elastase (NE) promoter through binding to their respective cis elements; cooperative activation is mediated via DNA-binding sites and likely involves a coactivator protein, as synergistic DNA binding between the factors could not be demonstrated in gel shift assays. Transient transfection reporter assays; gel shift (EMSA); mutational analysis of promoter elements; cell-line-specific assays Molecular and cellular biology Medium 8756629
2002 Crystal structures of c-Myb DBD and C/EBPbeta DBD bound to promoter DNA revealed that C/EBPbeta interacts with R2 of c-Myb bound to a separate DNA fragment, with intervening DNA looping; point mutations in v-Myb R2 eliminate this interaction. GST pulldown and AFM confirmed long-range protein-protein interaction and DNA looping. X-ray crystallography; GST pulldown; luciferase transactivation assay; atomic force microscopy Cell High 11792321
2004 Wnt-1 signal induces phosphorylation and proteasome-dependent degradation of c-Myb via the TAK1–HIPK2–NLK kinase cascade; NLK binds directly to c-Myb together with HIPK2, leading to c-Myb phosphorylation at multiple sites, followed by ubiquitination and degradation. Overexpression of NLK in M1 cells abrogates c-Myb's ability to maintain the undifferentiated state. Co-immunoprecipitation; in vitro kinase assays; proteasome inhibitor experiments; ubiquitination assays; M1 cell differentiation assay; overexpression studies Genes & development High 15082531
2000 p300 acetylates c-Myb at three lysine residues (K471, K480, K485) in the carboxyl-terminal conserved domain both in vitro and in vivo; acetylation dramatically increases c-Myb DNA binding activity and transactivation of mim-1 and CD34 promoters. The bromodomain of p300 is required for effective acetylation of c-Myb. In vitro acetyltransferase assay; in vivo acetylation detection; EMSA; luciferase reporter assay; site-directed mutagenesis (KA mutant) Oncogene High 10656693
2000 CBP acetylates c-Myb at K438 and K441 within its negative regulatory domain (NRD) in vitro, and in vivo at those and additional p300-induced sites; acetylation of these sites enhances c-Myb's association with CBP and synergistically increases c-Myb transactivation activity. The C/H2 domain of CBP directly interacts with the NRD of c-Myb. In vitro acetyltransferase assay; site-directed mutagenesis; transactivation reporter assays; co-immunoprecipitation; domain mapping The Journal of biological chemistry High 11073948
1986 The human c-myb gene product localizes to the nucleus and is associated with the nuclear matrix in leukemic cells. Immunostaining with antiserum generated against recombinant c-myb carboxyl-terminal protein; nuclear fractionation Science Medium 3014652
1988 c-myb protein degradation is energy-dependent, does not involve lysosomes or ubiquitin, and does not produce cleavage intermediates; heat shock increases c-myb protein half-life ~2-fold and reduces c-myb protein synthesis ~4-fold, with recovery being energy-dependent. Pulse-chase metabolic labeling; inhibitor studies (lysosomal, energy, ubiquitin); heat shock experiments; protein synthesis measurement Molecular and cellular biology Medium 3043180
1993 c-myb transactivates the human cdc2 gene promoter through two closely spaced Myb binding sites at -410 to -392 upstream of the transcription start site; mutations in the Myb binding sites abrogate c-myb-dependent CAT reporter activation. CAT reporter cotransfection; mutational analysis of Myb binding sites; electrophoretic mobility shift assay with bacterially expressed Myb protein The Journal of biological chemistry Medium 8420994
1991 Truncation of either the amino or carboxyl terminus of c-Myb is sufficient for transformation of chicken bone marrow cells; full-length c-Myb overexpression does not transform. The normal N- and C-termini of c-Myb suppress transformation when fused to v-Myb. Retroviral expression of truncated c-Myb constructs; transformation assay of primary chicken bone marrow cells; clonogenic assay Molecular and cellular biology High 2072904
2010 c-Myb is recruited to the MLL histone methyltransferase complex through menin, contributing to MLL-mediated H3K4 methylation; silencing MYB in human leukemic cells causes global decrease in H3K4 methylation, decreased HOXA9 and MEIS1 expression, and reduced MLL and menin occupancy at the HOXA9 locus. Co-immunoprecipitation; chromatin immunoprecipitation (ChIP); siRNA-mediated knockdown; methylation assays; H3K4me3 quantification The Journal of clinical investigation High 20093773
1993 c-Myb directly transactivates c-myc in a cell-lineage-dependent manner requiring direct DNA binding by Myb to Myb-binding sites in the c-myc promoter; de novo protein synthesis is not required for c-myc transactivation. Transient transfection reporter assays; S1 nuclease protection; mutational analysis; conditional c-Myb expression; cycloheximide inhibition Molecular and cellular biology Medium 8474446
1994 c-Myb transactivates the CD34 promoter via specific Myb binding sites in the 5' flanking region; constitutive c-Myb expression induces endogenous CD34 mRNA and surface antigen in CD34-negative glioblastoma cells. CAT reporter transfection; EMSA; northern blot; c-Myb overexpression in fibroblasts and glioblastoma cells The Journal of experimental medicine Medium 7509358
1998 c-Maf physically associates with c-Myb and inhibits c-Myb-dependent transcription of the myeloid CD13/APN gene promoter; formation of inhibitory Myb-Maf complexes is developmentally regulated, highest in immature myeloid cells. Co-immunoprecipitation; reporter gene assays; western blot; developmental stage-specific cell line analysis Molecular and cellular biology Medium 9566892
2005 TRAF7 binds to the DNA-binding domain of c-Myb via its WD40 repeats and stimulates c-Myb sumoylation at K523 and K499 (same sites as PIASy-induced sumoylation); sumoylated c-Myb is sequestered to the cytoplasm by TRAF7, inhibiting c-Myb transactivation activity. Co-immunoprecipitation; sumoylation assay; immunofluorescence localization; subcellular fractionation; transactivation reporter assays; site-directed mutagenesis Molecular biology of the cell High 16162816
2007 c-Myb directly activates Gata3 transcription, and is required for upregulation of Gata3 in response to TCR signaling during positive selection; loss of c-Myb causes fewer helper T cells and gain-of-function c-Myb transgene blocks cytotoxic T cell development. Conditional c-Myb knockout and c-Myb transgenic mice; reporter gene assays demonstrating Gata3 as direct c-Myb target; flow cytometric analysis of T cell development The EMBO journal High 17641686
2010 c-myb directly transactivates KLF1 and LMO2 promoters (demonstrated by ChIP and luciferase reporter assay) to support erythropoiesis; c-myb silencing in human CD34+ cells shifts fate toward megakaryocyte at expense of erythroid lineage, and this defect is rescued by KLF1 or LMO2 overexpression. siRNA knockdown; chromatin immunoprecipitation; luciferase reporter assay; retroviral rescue experiments; clonogenic assay; flow cytometry Blood High 20686118
2007 miR-150 controls B cell differentiation by targeting c-Myb in a dose-dependent manner; gain and loss of miR-150 show that its effect on lymphocyte development is mediated through c-Myb, with combined c-Myb conditional/partial ablation confirming the miR-150–c-Myb epistasis. miR-150 loss-of-function (knockout) and gain-of-function (transgenic) mouse models; conditional c-Myb ablation; flow cytometric analysis Cell High 17923094
2019 c-Myb acts as a transcriptional activator of Tcf7 (Tcf1) to enhance CD8+ T cell memory development and as a repressor of Zeb2 to inhibit effector differentiation; the transactivation domain is necessary for restraining differentiation while the negative regulatory domain is critical for cell survival. Conditional c-Myb knockout; c-Myb overexpression; domain mutagenesis experiments; adoptive transfer; viral infection models; gene expression analysis Nature immunology High 30778251
2010 c-Myb promotes survival of CD4+CD8+ double-positive thymocytes by upregulating Bcl-xL; conditional deletion causes premature apoptosis of small preselection DP thymocytes independently of TCR signaling, and forced Bcl-xL expression rescues survival while c-Myb re-expression restores both Bcl-xL expression and the DP compartment. Conditional c-Myb knockout; Bcl-xL retroviral rescue; c-Myb retroviral rescue; apoptosis assays; Tcra repertoire analysis Journal of immunology High 20142358
1999 c-Myb is required for early T cell development; deletion of c-Myb causes a complete block just before the oligopotent thymocyte matures into the definitive T cell precursor. Homozygous null c-Myb/Rag1 chimeric mice; flow cytometric analysis of thymocyte populations Genes & development High 10323859
2005 c-Myb is required for B cell development at the pro-B to pre-B cell transition; loss of c-Myb prevents normal B cell homeostasis by decreasing splenic B cell survival, associated with hyporesponsiveness to BLyS, decreased BR3 expression, and altered PKCdelta nuclear accumulation. Tissue-specific (conditional) Myb inactivation; flow cytometry; survival assays; BLyS receptor expression analysis; PKCdelta localization studies Immunity High 16169500
2009 c-Myb is absolutely required for differentiation of CD19+ B-lineage cells, controlling intrinsic survival and proper expression of IL-7 receptor alpha (CD127) and Ebf1; survival of c-Myb-deficient pro-B cells cannot be rescued by CD127 retroviral transduction, but B cell differentiation can be partially rescued by exogenous Ebf1. Tissue-specific Myb inactivation (Mb1-cre); retroviral rescue experiments; stromal cell culture; flow cytometry Journal of immunology High 19843942
2002 c-Myb and Pax-5 cooperatively bind to and activate the RAG-2 promoter in immature B cells through synergistic DNA binding; the C-terminus of c-Myb mediates physical interaction with Pax-5, and dominant-negative c-Myb suppresses RAG-2 promoter activity. Reporter gene assays; EMSA; co-immunoprecipitation; dominant-negative mutant experiments; deletion analysis Blood Medium 11781241
1993 Casein kinase II (CKII) phosphorylates c-Myb at Ser-11 and Ser-12; replacing these serines with alanine increases DNA-binding affinity (up to 10-fold reduced dissociation constant) and increases transactivation activity on mim-1 and synthetic promoters. In vitro kinase assay; site-directed mutagenesis; EMSA with dissociation constant measurement; transactivation reporter assays Cellular & molecular biology research Medium 7735324
1993 p42mapk (ERK2) phosphorylates avian and murine c-Myb but not AMV v-Myb in vitro on serine and threonine residues mapping to the C-terminal negative regulatory domain. In vitro kinase assay with bacterially expressed Myb proteins; phosphoamino acid analysis; deletion mapping Oncogene Medium 8336948
2000 Phosphorylation of c-Myb by Ser/Thr kinases (inhibited by okadaic acid) leads to hyperphosphorylation causing conformational changes and extremely rapid proteasome-dependent degradation; Ser/Thr phosphatases normally prevent the conformational changes that target c-Myb for degradation. The hyperphosphorylated form retains DNA binding activity. Okadaic acid phosphatase inhibitor treatment; pulse-chase protein stability assay; proteasome inhibitor; EMSA; phosphoamino acid analysis; antibody conformational recognition assay Oncogene Medium 10851088
2017 Mebendazole induces c-MYB protein degradation via the proteasome by interfering with the HSP70 chaperone system, inhibiting AML colony formation in vitro and AML progression in mouse xenotransplantation in vivo. Proteasome inhibitor rescue experiments; HSP70 inhibition assays; colony formation assay; mouse xenotransplantation; gene expression signature analysis Leukemia Medium 29089643
2022 Withaferin A (WFA) induces rapid c-MYB protein ablation by disrupting HSP70/HSC70 chaperone protein homeostasis via proteotoxicity and the unfolded protein response; anti-AML activity of WFA depends on c-MYB modulation and can be partially reversed by a stabilized c-MYB mutant. Proteasome inhibitor rescue; stabilized c-MYB mutant rescue; western blot; colony formation assay; disease progression assay Leukemia Medium 35368048
2008 Pin1 physically interacts with c-Myb in a phosphorylation-dependent manner at S528 (within the EVES motif), and this interaction increases c-Myb transactivation activity in a manner dependent on Pin1 catalytic activity; Pin1 interaction does not increase c-Myb DNA binding. Co-immunoprecipitation; site-directed mutagenesis; transactivation reporter assays; DNA-binding assays; mass spectrometry confirming S528 phosphorylation in vivo Biochimica et biophysica acta Medium 18359295
2000 c-Myb and GATA-1 mutually inhibit each other's transcriptional activity through competitive binding to CBP; c-Myb, GATA-1, and CBP can form bipartite complexes but not a tripartite complex, with exclusive CBP binding being the molecular basis for mutual inhibition. Co-immunoprecipitation; transactivation reporter assays; domain mapping Oncogene Medium 10644988
2010 c-myb loss-of-function (missense I181N in the DNA recognition helix of repeat 3) in zebrafish abolishes definitive hematopoiesis while leaving primitive hematopoiesis intact, confirming evolutionary conservation of c-myb's essential role in definitive hematopoiesis across vertebrates. ENU mutagenesis; identification of c-myb(t25127) missense allele; zebrafish phenotypic analysis; genetic complementation Proceedings of the National Academy of Sciences High 20823231
2008 c-Myb-null embryonic stem cells fail to produce embryoid bodies with spontaneously contracting smooth muscle cells; mesodermal differentiation is unaffected but myocardin upregulation and SMC-specific gene expression (smooth muscle alpha-actin, SM22alpha, SMMHC) are impaired; c-myb-/- cells show reduced contribution to SMC lineage in chimeric embryos and aortas. c-myb-/- ES cell differentiation to embryoid bodies; RT-PCR; flow cytometry; chimeric embryo analysis; aorta chimerism assessment Circulation research Medium 18187733
2007 c-Myb is required for normal progenitor cell homeostasis in colonic crypts; hypomorphic c-myb mutations targeting DNA binding, transactivation, or negative regulatory domains all reduce colonic crypt size through a progenitor proliferation defect mediated in part by reduced Cyclin E1 expression; tissue-specific adult colon deletion confirms requirement for crypt integrity and differentiation. Three distinct hypomorphic c-myb mouse strains; tissue-specific adult colon c-myb deletion; BrdU proliferation assay; cyclin E1 expression analysis Proceedings of the National Academy of Sciences High 17360438
2017 c-Myb activates the miR-200 family (miR-200b, miR-200a, miR-429, miR-200c, miR-141) by binding to Myb binding sites in their promoter regions; when co-expressed with ZEB1, ZEB1 repression dominates over c-Myb activation; promoter methylation during TGF-β-induced EMT overrides c-Myb-dependent activation. Ectopic expression and gene silencing; luciferase reporter assay with Myb binding site mutations; ChIP; bisulfite sequencing Cell cycle Medium 24067373
2008 Alternative splicing of human c-myb produces a family of transcripts (using alternate exons 8A, 9A, 9B, 10A, 13A, 14A) encoding c-Myb proteins with identical DNA binding domains but unique C-terminal domains; these variant proteins exhibit quantitative and qualitative differences in transcriptional activities and specificities. Quantitative RT-PCR; polysome association assay; transactivation reporter assays; expression analysis in human leukemia samples Molecular and cellular biology Medium 18195038
2017 c-Myb represses T-bet expression in mature B cells to limit aberrant IgG2c/CXCR3/plasma cell differentiation during germinal center responses; deletion of c-Myb increases T-bet expression and results in aberrant plasma cell differentiation within the germinal center mediated by CXCR3. Conditional c-Myb deletion in mature B cells; flow cytometry; serum Ig quantification; gene expression analysis Cell reports Medium 28423310
2015 c-Myb is required for plasma cell migration to bone marrow; in the absence of c-Myb, c-Myb-deficient plasma cells fail to migrate along a CXCL12 gradient, resulting in absence of IgG+ antigen-specific plasma cells in bone marrow after immunization or infection. Conditional c-Myb deletion; in vitro migration assay to CXCL12; immunization and viral infection models; flow cytometry The Journal of experimental medicine High 26077717
2011 c-Myb binds the Bmi1 promoter and activates its transcription; c-Myb and Bmi1 are required for p190BCR/ABL-dependent B-cell leukemogenesis, and ectopic Bmi1 expression can partially rescue the proliferative defect caused by c-Myb loss. Co-immunoprecipitation; ChIP; luciferase reporter assay; knockdown; retroviral rescue; in vivo leukemia model Leukemia Medium 21960247
2017 c-Myb functions as a pioneer transcription factor; each repeat of the c-Myb DNA-binding domain binds histones, and the D152V mutation in repeat 3 disrupts histone binding, impairs chromatin opening (ATAC-seq), and abrogates c-Myb's ability to regulate differentiation-associated genes. ATAC-seq; histone binding assay; site-directed mutagenesis (D152V); transcriptome analysis; chromatin accessibility assay in K562 cells Nucleic acids research High 28472346
1996 An intact c-Myb binding site in the TCR-delta intronic enhancer (Edelta) is necessary for efficient VDJ recombination at the TCR-delta locus in vivo; transgenic minilocus recombination substrate with mutated Myb binding site in Edelta shows markedly reduced rearrangement. Transgenic mouse minilocus recombination substrate; mutation of Myb binding site in Edelta; PCR analysis of VDJ rearrangements The Journal of experimental medicine High 8551234
1995 Phosphorylation of c-Myb at Ser-11 and Ser-12 positively modulates DNA binding by overcoming the negative regulatory influence of the leucine zipper (LZ); LZ mutation or phosphorylation both enhance DNA binding activity, and phosphatase treatment reduces DNA binding of insect-cell-expressed c-Myb. In vitro binding assays with E. coli-expressed c-Myb proteins; CKII and PKA kinase assays; phosphatase treatment; insect cell expression; site-directed mutagenesis Oncogene Medium 7478531

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell 968 1709592
2007 MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 841 17923094
1988 Constitutive expression of a c-myb cDNA blocks Friend murine erythroleukemia cell differentiation. Molecular and cellular biology 334 2832742
1996 CBP as a transcriptional coactivator of c-Myb. Genes & development 317 8598284
2005 c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation. Developmental cell 236 15691758
1998 Pim-1 kinase and p100 cooperate to enhance c-Myb activity. Molecular cell 218 9809063
1996 C/EBP, c-Myb, and PU.1 cooperate to regulate the neutrophil elastase promoter. Molecular and cellular biology 209 8756629
1984 Aberrant expression of an amplified c-myb oncogene in two cell lines from a colon carcinoma. Proceedings of the National Academy of Sciences of the United States of America 192 6589609
1983 Chromosomal sublocalization of human c-myb and c-fes cellular onc genes. Nature 173 6866112
1988 c-myc and c-myb protein degradation: effect of metabolic inhibitors and heat shock. Molecular and cellular biology 157 3043180
2019 The transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity. Nature immunology 153 30778251
1996 The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb. Genes & development 153 8756344
2005 c-Myb is critical for B cell development and maintenance of follicular B cells. Immunity 151 16169500
2004 Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK. Genes & development 146 15082531
1986 Studies of the human c-myb gene and its product in human acute leukemias. Science (New York, N.Y.) 142 3014652
2002 Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter. Cell 133 11792321
1999 c-Myb is essential for early T cell development. Genes & development 132 10323859
1991 Expression of c-myb and B-myb, but not A-myb, correlates with proliferation in human hematopoietic cells. Blood 132 1984793
1992 Inhibition of leukemia cell proliferation by receptor-mediated uptake of c-myb antisense oligodeoxynucleotides. Proceedings of the National Academy of Sciences of the United States of America 131 1495997
2010 Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved. Proceedings of the National Academy of Sciences of the United States of America 121 20823231
1985 Expression of the c-myb oncogene in human small cell lung carcinoma. Cancer research 119 2578097
1993 c-myb transactivates cdc2 expression via Myb binding sites in the 5'-flanking region of the human cdc2 gene. The Journal of biological chemistry 115 8420994
1984 Autoimmunity and increased c-myb transcription. Science (New York, N.Y.) 115 6494925
1990 Strong association between c-myb and oestrogen-receptor expression in human breast cancer. Oncogene 113 2181374
2000 c-Myb acetylation at the carboxyl-terminal conserved domain by transcriptional co-activator p300. Oncogene 108 10656693
1991 Protein truncation is required for the activation of the c-myb proto-oncogene. Molecular and cellular biology 105 2072904
2010 c-Myb binds MLL through menin in human leukemia cells and is an important driver of MLL-associated leukemogenesis. The Journal of clinical investigation 104 20093773
2008 Critical roles for c-Myb in hematopoietic progenitor cells. Seminars in immunology 103 18585056
1987 Relationship between the c-myb locus and the 6q-chromosomal aberration in leukemias and lymphomas. Science (New York, N.Y.) 103 3469751
1988 Regulation of c-myb expression in human neuroblastoma cells during retinoic acid-induced differentiation. Molecular and cellular biology 97 3380093
2010 c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression. Blood 93 20686118
2007 c-Myb is required for progenitor cell homeostasis in colonic crypts. Proceedings of the National Academy of Sciences of the United States of America 93 17360438
2008 c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development. Molecular biology and evolution 92 18667440
2017 Targeting acute myeloid leukemia by drug-induced c-MYB degradation. Leukemia 90 29089643
2000 c-MYB oncogene-like genes encoding three MYB repeats occur in all major plant lineages. The Plant journal : for cell and molecular biology 87 10743663
1993 Mechanism of c-myc regulation by c-Myb in different cell lineages. Molecular and cellular biology 85 8474446
1994 Regulation of the expression of the hematopoietic stem cell antigen CD34: role of c-myb. The Journal of experimental medicine 81 7509358
1993 Transcription regulation by murine B-myb is distinct from that by c-myb. Nucleic acids research 81 8382794
2000 Increased affinity of c-Myb for CREB-binding protein (CBP) after CBP-induced acetylation. The Journal of biological chemistry 77 11073948
2011 Identification and regulation of c-Myb target genes in MCF-7 cells. BMC cancer 76 21261996
2003 Targeting c-Myb expression in human disease. Expert opinion on therapeutic targets 76 12667100
1986 Regulated expression of the c-myb and c-myc oncogenes during erythroid differentiation. Journal of cellular biochemistry 74 3464612
1998 c-Maf interacts with c-Myb to regulate transcription of an early myeloid gene during differentiation. Molecular and cellular biology 72 9566892
1997 GABP cooperates with c-Myb and C/EBP to activate the neutrophil elastase promoter. Blood 72 9192779
1997 c-Myb and Ets proteins synergize to overcome transcriptional repression by ZEB. The EMBO journal 71 9233802
1992 Expression of the c-myb proto-oncogene in bovine vascular smooth muscle cells. The Journal of biological chemistry 71 1537845
1995 Expression of mouse c-myb during embryonic development. Oncogene 70 8570177
1989 Characterization of alternate and truncated forms of murine c-myb proteins. Oncogene research 70 2549488
2004 Requirement of c-myb in T cell development and in mature T cell function. Proceedings of the National Academy of Sciences of the United States of America 69 15466706
2017 miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb. Cell reports 65 28903040
2006 Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development. Blood 65 16597594
2006 Transgene insertion in proximity to the c-myb gene disrupts erythroid-megakaryocytic lineage bifurcation. Molecular and cellular biology 63 16940183
1989 Expression of protooncogene c-myb in normal human hematopoietic cells. Blood 63 2469491
2008 Thrombopoietin regulates c-Myb expression by modulating micro RNA 150 expression. Experimental hematology 61 18814950
2007 c-Myb regulates lineage choice in developing thymocytes via its target gene Gata3. The EMBO journal 61 17641686
2010 Critical roles for c-Myb in lymphoid priming and early B-cell development. Blood 59 20130238
2007 Collagen loss and impaired wound healing is associated with c-Myb deficiency. The Journal of pathology 59 17152050
2010 Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb. Leukemia 55 21079614
1994 Regulation of transcription factors c-Myc, Max, and c-Myb by casein kinase II. Cellular & molecular biology research 55 7735324
2017 c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses. Cell reports 54 28423310
2009 c-Myb is required for pro-B cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 51 19843942
2005 Anomalous megakaryocytopoiesis in mice with mutations in the c-Myb gene. Blood 51 15665109
2005 TRAF7 sequesters c-Myb to the cytoplasm by stimulating its sumoylation. Molecular biology of the cell 51 16162816
2008 Requirement of c-Myb for p210(BCR/ABL)-dependent transformation of hematopoietic progenitors and leukemogenesis. Blood 49 18227349
1999 c-Myb is critical for murine colon development. Oncogene 49 10523863
1997 c-Myb trans-activates the human DNA topoisomerase IIalpha gene promoter. The Journal of biological chemistry 48 9045645
2000 Inhibitory interaction of c-Myb and GATA-1 via transcriptional co-activator CBP. Oncogene 47 10644988
2008 Alternative RNA splicing produces multiple forms of c-Myb with unique transcriptional activities. Molecular and cellular biology 46 18195038
2010 c-Myb promotes the survival of CD4+CD8+ double-positive thymocytes through upregulation of Bcl-xL. Journal of immunology (Baltimore, Md. : 1950) 45 20142358
2013 Activation of miR200 by c-Myb depends on ZEB1 expression and miR200 promoter methylation. Cell cycle (Georgetown, Tex.) 42 24067373
2016 c-myb hyperactivity leads to myeloid and lymphoid malignancies in zebrafish. Leukemia 40 27457538
1995 Enforced expression of full length c-Myb leads to density-dependent transformation of murine haemopoietic cells. Oncogene 40 7478588
2011 c-Myb and its target Bmi1 are required for p190BCR/ABL leukemogenesis in mouse and human cells. Leukemia 39 21960247
2019 c-MYB and DMTF1 in Cancer. Cancer investigation 38 30599775
1998 The c-Myb oncoprotein. The international journal of biochemistry & cell biology 38 9693954
1996 Regulation of T cell receptor delta gene rearrangement by c-Myb. The Journal of experimental medicine 38 8551234
1998 Truncated c-Myb expression in the human leukemia cell line TK-6. Leukemia 37 9737692
1993 c-Myb and v-Myb are differentially phosphorylated by p42mapk in vitro. Oncogene 35 8336948
2015 c-Myb is required for plasma cell migration to bone marrow after immunization or infection. The Journal of experimental medicine 34 26077717
2008 c-Myb-dependent smooth muscle cell differentiation. Circulation research 34 18187733
2013 MicroRNA-150 aggravates H2O2-induced cardiac myocyte injury by down-regulating c-myb gene. Acta biochimica et biophysica Sinica 33 23824072
2020 Resveratrol Activates Natural Killer Cells through Akt- and mTORC2-Mediated c-Myb Upregulation. International journal of molecular sciences 32 33339133
2016 c-Myb acts in parallel and cooperatively with Cebp1 to regulate neutrophil maturation in zebrafish. Blood 32 27268086
1989 c-myc and c-myb oncoproteins during induced maturation of myeloid and erythroid human leukemic cell lines. Cancer research 32 2684403
1992 The PR264/c-myb connection: expression of a splicing factor modulated by a nuclear protooncogene. Proceedings of the National Academy of Sciences of the United States of America 30 1465383
2018 The activation of microRNA-520h-associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression. Cell death & disease 29 30158641
1995 Regulation of c-Myb through protein phosphorylation and leucine zipper interactions. Oncogene 29 7478531
2017 A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function. Nucleic acids research 28 28472346
2002 Cooperative binding of c-Myb and Pax-5 activates the RAG-2 promoter in immature B cells. Blood 28 11781241
2002 Runx1, c-Myb, and C/EBPalpha couple differentiation to proliferation or growth arrest during hematopoiesis. Journal of cellular biochemistry 28 12210729
2000 Hyperphosphorylation and increased proteolytic breakdown of c-Myb induced by the inhibition of Ser/Thr protein phosphatases. Oncogene 27 10851088
2022 Identification of a c-MYB-directed therapeutic for acute myeloid leukemia. Leukemia 26 35368048
2008 Pin1 interacts with c-Myb in a phosphorylation-dependent manner and regulates its transactivation activity. Biochimica et biophysica acta 26 18359295
2015 C-myb Regulates Autophagy for Pulp Vitality in Glucose Oxidative Stress. Journal of dental research 25 26661713
2013 Gene delivery of c-myb increases bone formation surrounding oral implants. Journal of dental research 25 23838059
2005 The role of c-MYB in benzene-initiated toxicity. Chemico-biological interactions 25 15935814
1992 c-myc and c-myb expression in acute myelogenous leukemia. Leukemia research 25 1405703
2016 MicroRNA-503 represses epithelial-mesenchymal transition and inhibits metastasis of osteosarcoma by targeting c-myb. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 24 26768615
2001 Constitutive expression of c-myb mRNA in the adult rat brain. Brain research 24 11172765
1992 Defective c-myc and c-myb RNA turnover in acute myeloid leukemia cells. Blood 24 1371419

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