Affinage

MYB

Transcriptional activator Myb · UniProt P10242

Length
640 aa
Mass
72.3 kDa
Annotated
2026-04-29
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYB encodes c-Myb, a sequence-specific transcription factor essential for definitive hematopoiesis, lymphocyte developmental checkpoints, and progenitor cell homeostasis in multiple tissues including colonic crypts and smooth muscle (PMID:1709592, PMID:15195090, PMID:17360438, PMID:18187733). c-Myb binds DNA through a tripartite repeat domain (R1R2R3) that also functions as a pioneer factor capable of opening chromatin, and it activates transcription of key targets—including c-MYC, GATA3, and HOXA9—by recruiting the coactivators CBP/p300 and p100, while corepressor complexes (TIF1β/Ski/N-CoR/HDAC, BS69, TIP60) attenuate its activity through the C-terminal negative regulatory domain (PMID:8598284, PMID:10688644, PMID:17641686, PMID:20093773, PMID:14761981, PMID:28472346). The protein is tightly regulated post-translationally: CBP acetylation at K438/K441 enhances transactivation, MAPK phosphorylation at S528 within the EVES motif suppresses it, Fbxw7/NLK-dependent ubiquitination and HSP70 chaperone-dependent pathways direct proteasomal degradation, TRAF7-mediated sumoylation sequesters c-Myb in the cytoplasm, and miR-150 controls c-Myb protein levels to tune lymphocyte development (PMID:11073948, PMID:7604007, PMID:18765672, PMID:16162816, PMID:17923094). Oncogenic activation requires loss of N- or C-terminal negative regulatory domains and depends on intact CBP/p300 interaction (PMID:2072904, PMID:19737967).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1987 High

    Before the mechanism of c-myb downregulation in mature B cells was known, nuclear run-on assays revealed that a regulated block to transcriptional elongation within the first intron—correlated with chromatin structure changes—controls c-myb expression during B cell maturation, establishing that c-myb is regulated at the elongation rather than initiation step.

    Evidence Nuclear run-on transcription and DNase I hypersensitivity assays in pre-B vs. mature B lymphoma lines

    PMID:3498214

    Open questions at the time
    • Identity of trans-acting factors mediating elongation block unknown
    • Whether the elongation block operates in non-B lineages not tested
  2. 1989 High

    The cellular function of c-Myb was unknown beyond its viral oncogene origin; antisense knockdown and reporter assays demonstrated that c-Myb is a sequence-specific transcriptional activator required for hematopoietic colony formation and G1/S cell cycle progression in T lymphocytes, establishing its core identity as a proliferation-coupled transcription factor.

    Evidence Antisense oligonucleotide knockdown in bone marrow and T cells; cotransfection CAT reporter assays

    PMID:2461588 PMID:2536148 PMID:2665077

    Open questions at the time
    • Direct transcriptional targets not yet identified
    • Whether c-Myb activates or represses genes was only partially resolved
  3. 1991 High

    Whether c-Myb was truly essential in vivo for hematopoiesis was resolved by knockout mice that died of severe anemia from failure of fetal liver definitive hematopoiesis while primitive yolk-sac erythropoiesis was unaffected, and structure-function studies showed that truncation of either terminus converts c-Myb into a transforming oncoprotein, establishing that N- and C-terminal domains restrain oncogenic activity.

    Evidence Homologous recombination knockout mouse; retroviral transformation assays with truncation mutants in primary bone marrow

    PMID:1709592 PMID:2072904

    Open questions at the time
    • Mechanism of N-terminal negative regulation unclear
    • Whether the C-terminal negative regulatory domain acts through intramolecular folding or cofactor recruitment not yet determined
  4. 1992 High

    How the C-terminal negative regulatory domain (NRD) suppresses transactivation was addressed by fusion protein assays showing it inhibits both in cis and in trans, independently of DNA binding, via protein-protein interactions targeting the minimal activation domain.

    Evidence GAL4/LexA/VP16 fusion transactivation assays with deletion mutagenesis

    PMID:1340467

    Open questions at the time
    • Identity of NRD-binding partners not yet known
    • Whether intramolecular folding contributes to NRD function not resolved
  5. 1996 High

    The coactivator mechanism was elucidated when CBP was identified as a direct binding partner of c-Myb's transactivation domain, and the EVES motif in the C-terminus was shown to mediate intramolecular interaction with the DNA-binding domain and intermolecular interaction with the coactivator p100, linking the NRD to a specific autoinhibitory and coactivator-recruitment mechanism.

    Evidence Yeast two-hybrid; in vitro binding; cotransfection transactivation assays; antisense CBP RNA

    PMID:8598284 PMID:8756344

    Open questions at the time
    • Structural basis of intramolecular folding not determined
    • Relative contributions of CBP vs. p100 to c-Myb activity in vivo unknown
  6. 2000 High

    Post-translational regulation was defined at two levels: CBP was found to acetylate c-Myb at K438/K441 within the NRD to enhance transactivation by increasing CBP affinity, and c-Myb was shown to directly activate c-MYC transcription as a key proliferative target, while competition between c-Myb and GATA-1 for CBP binding established a mechanism for lineage-specific gene regulation.

    Evidence In vitro acetylation with mass spectrometry; conditional MybER activation with cycloheximide; competitive co-IP between c-Myb, GATA-1, and CBP

    PMID:10644988 PMID:10688644 PMID:11073948

    Open questions at the time
    • Whether acetylation occurs in physiological hematopoietic cells not shown
    • Full repertoire of direct target genes unknown
  7. 2002 High

    Structural insight into how c-Myb cooperates with partner transcription factors came from crystal structures showing c-Myb R2 contacts DNA-bound C/EBPβ on a separate DNA element with intervening loop formation, and functional studies demonstrated cooperative c-Myb/Pax-5 binding at the RAG-2 promoter in B cells.

    Evidence X-ray crystallography; GST pull-down; AFM imaging; co-IP and reporter assays for Pax-5 interaction

    PMID:11781241 PMID:11792321

    Open questions at the time
    • Whether DNA looping is a general feature of c-Myb target gene regulation unknown
    • Structural basis of c-Myb/Pax-5 interaction not resolved
  8. 2004 High

    The corepressor mechanism was defined when TIF1β was found to bind the NRD and recruit Ski/N-CoR/mSin3A/HDAC, with Ski competing with CBP, explaining how oncogenic v-Myb NRD mutations escape repression; simultaneously, conditional deletion at defined thymocyte stages revealed c-Myb is required at three distinct T cell developmental checkpoints.

    Evidence Co-IP, GST pull-down, and HDAC recruitment assays; Cre-lox tissue-specific conditional knockout with flow cytometry

    PMID:14761981 PMID:15195090

    Open questions at the time
    • Whether TIF1β and CBP/p300 occupy the same target promoters in vivo not tested by ChIP
    • Which c-Myb target genes mediate each thymocyte checkpoint not identified
  9. 2005 High

    Cytoplasmic sequestration as a regulatory mechanism was established when TRAF7 was shown to promote sumoylation of c-Myb at K499 and K523, relocating it to the cytoplasm and inhibiting transactivation, while a PI3K/Akt pathway was found to stabilize c-Myb protein by suppressing proteasomal degradation.

    Evidence Co-IP; sumoylation assay; subcellular fractionation; PI3K/Akt inhibitors with pulse-chase

    PMID:15927960 PMID:16162816

    Open questions at the time
    • Whether sumoylation and ubiquitination are coordinated or mutually exclusive not determined
    • Specific E3 ligase for Akt-regulated degradation pathway not identified at this point
  10. 2007 High

    miR-150 was identified as a physiological rheostat controlling c-Myb protein levels in vivo, with dose-dependent effects on B and T lymphocyte development; c-Myb was also shown to directly activate Gata3 transcription downstream of TCR signaling to drive helper T cell differentiation, and to be required for colonic crypt progenitor homeostasis via Cyclin E1.

    Evidence Genetic epistasis with miR-150 and conditional c-myb ablation in mice; ChIP and conditional knockout for Gata3; hypomorphic and conditional knockout in intestine

    PMID:17360438 PMID:17641686 PMID:17923094

    Open questions at the time
    • Whether other miRNAs cooperate with miR-150 to regulate c-Myb in vivo not addressed
    • Full set of c-Myb targets in intestinal progenitors unknown
  11. 2008 High

    The ubiquitin-proteasome degradation pathway was molecularly defined when Fbxw7 was identified as the E3 ligase targeting c-Myb for NLK-phosphorylation-dependent ubiquitination—explaining v-Myb's resistance to degradation—and Pin1 isomerase was found to bind phospho-S528 in the EVES motif to modulate transactivation; alternative splicing generating multiple c-Myb isoforms with distinct activities was also characterized.

    Evidence In vitro ubiquitination reconstitution; co-IP; siRNA; Pin1 mutagenesis; RT-PCR splicing and reporter analysis

    PMID:18195038 PMID:18359295 PMID:18765672

    Open questions at the time
    • Whether Fbxw7-mediated degradation is the dominant pathway in all hematopoietic lineages not determined
    • Functional significance of individual splice isoforms in vivo not established
  12. 2010 High

    c-Myb's role expanded beyond conventional hematopoiesis when it was shown to recruit to the MLL complex via menin to regulate H3K4 methylation and HOXA9/MEIS1 expression in MLL-rearranged leukemia, and to prime iNKT cell development by simultaneously controlling CD1d, SLAM receptors, and DP thymocyte survival.

    Evidence Co-IP; ChIP for MLL/menin/H3K4me3; siRNA; conditional knockout with flow cytometry for iNKT

    PMID:20093773 PMID:20383148

    Open questions at the time
    • Whether c-Myb is a stable MLL complex subunit or a transient recruiter unclear
    • Structural basis of menin-c-Myb interaction not resolved
  13. 2017 High

    Pioneer factor activity of c-Myb was established when the D152V mutation in R3 was shown to disrupt histone binding, impairing chromatin opening at specific loci as measured by ATAC-seq and selectively affecting differentiation genes; separately, pharmacological disruption of HSP70 chaperone homeostasis was shown to destabilize c-Myb protein and inhibit AML.

    Evidence ATAC-seq; histone-binding assay; site-directed mutagenesis; proteasome inhibitor rescue and xenotransplantation

    PMID:28472346 PMID:29089643

    Open questions at the time
    • Genome-wide map of c-Myb pioneer sites in normal hematopoietic cells not available
    • Whether chaperone-dependent degradation pathway is distinct from Fbxw7 pathway not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full genome-wide catalog of direct c-Myb targets across hematopoietic lineages, the structural basis of the autoinhibitory intramolecular fold, how multiple post-translational modifications are coordinated on a single c-Myb molecule, and whether the pioneer factor function identified via R3 histone binding is required for all or only a subset of c-Myb's developmental roles.
  • No high-resolution full-length c-Myb structure available
  • Coordination of acetylation, phosphorylation, sumoylation, and ubiquitination on the same molecule not studied
  • Pioneer function not tested in primary hematopoietic stem/progenitor cells

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 6 R-HSA-168256 Immune System 5 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2
Partners
CREBBPFBXW7KAT5PAX5PIM1SKITRAF7TRIM28
Complex memberships
MLL/menin complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 c-myb is required for definitive (adult-type) hematopoiesis in the fetal liver; homologous recombination knockout in mice causes severe anemia by day 15 due to failure of fetal liver hematopoiesis, while primitive yolk-sac erythropoiesis is unaffected, placing c-Myb as essential for maintaining proliferative state of hematopoietic progenitor cells. Homologous recombination knockout mouse; hematopoietic colony analysis Cell High 1709592
1988 c-Myb protein is required for normal human hematopoietic colony formation; antisense oligodeoxynucleotides targeting c-myb mRNA decreased both colony size and number in bone marrow cultures without affecting residual cell maturation. Antisense oligodeoxynucleotide knockdown; hematopoietic colony formation assay Science High 2461588
1989 c-Myb protein is required for G1/S cell cycle transition in human T lymphocytes; antisense c-myb oligomer blocked T lymphocyte proliferation and decreased histone H3 mRNA and DNA content without affecting activation markers or c-myc expression, indicating a specific role in late G1/early S phase. Antisense oligomer knockdown; cell cycle analysis; marker expression profiling Science High 2665077
1989 c-Myb functions as a transcriptional trans-activator; mouse c-Myb protein stimulated transcription ~20-fold from a promoter containing tandem SV40 enhancer elements in cotransfection assays, demonstrating sequence-specific transcriptional activation. Cotransfection with CAT reporter; transactivation assay Nucleic Acids Research High 2536148
1989 c-Myb also mediates transcriptional repression; it binds a second low-affinity site (MBS-II) in the SV40 enhancer and competes with another transactivator to repress transcription, demonstrating bidirectional transcriptional regulation. Cotransfection with CAT reporter; mutational analysis of binding sites Nucleic Acids Research Medium 2552408
1996 CBP (CREB-binding protein) is a transcriptional coactivator of c-Myb; CBP directly binds the transcriptional activation domain of c-Myb in a phosphorylation-independent manner in vitro and in a yeast two-hybrid assay, stimulates c-Myb-dependent transcription, and its antisense suppresses c-Myb-induced activation; adenovirus E1A, which binds CBP, also inhibits c-Myb-induced transactivation. In vitro binding assay; yeast two-hybrid; antisense RNA; cotransfection transactivation assay Genes & Development High 8598284
2000 CBP acetylates c-Myb at Lys438 and Lys441 within the negative regulatory domain (NRD) via its C/H2 domain; acetylation enhances c-Myb's transactivation capacity by increasing its affinity for CBP. Mutation of all acetylation sites dramatically decreased trans-activating capacity. In vitro acetylation assay; mass spectrometry; site-directed mutagenesis; transactivation assay Journal of Biological Chemistry High 11073948
2002 Crystal structures of c-Myb and v-Myb DNA-binding domains in complex with C/EBPβ DBD and promoter DNA revealed that a DNA-bound C/EBPβ interacts with R2 of c-Myb bound to a separate DNA fragment; point mutations in v-Myb R2 eliminate this interaction. Confirmed by GST pull-down, luciferase assay, and atomic force microscopy showing intervening DNA looping. X-ray crystallography; GST pull-down; luciferase transactivation assay; atomic force microscopy Cell High 11792321
1996 The EVES motif in the c-Myb C-terminus mediates intramolecular interaction with the N-terminal DNA-binding domain and intermolecular interaction with p100 coactivator. p100 interacts with c-Myb and influences its transcriptional activity; the EVES motif contains a phosphorylation site important for negative regulation. Yeast two-hybrid; in vitro interaction assay; cotransfection transactivation assay Genes & Development High 8756344
1992 The c-Myb carboxyl terminus contains negative regulatory domains that inhibit transcriptional activation both in cis and in trans; the in-trans suppression is independent of c-Myb DNA binding and likely involves protein-protein interaction targeting the minimal transcriptional activation domain. GAL4/LexA/VP16 fusion transactivation assays; deletion mutagenesis Genes & Development High 1340467
1991 Truncation of either the N- or C-terminus of c-Myb is sufficient to activate its transforming ability in chicken bone marrow cells; full-length c-Myb overexpression does not transform. The normal termini suppress transformation when fused to v-Myb. Retroviral infection of primary bone marrow; transformation assay Molecular and Cellular Biology High 2072904
1995 Phosphorylation of c-Myb at serine-528 by p42 MAPK within the negative regulatory domain negatively modulates its transcriptional activation; substitution of Ser-528 to Ala increased c-Myb transactivation 2–7-fold. Three in-vitro phosphorylated peptides comigrated with metabolically labeled c-Myb peptides from MEL cells. In vitro kinase assay; mass spectrometry; site-directed mutagenesis; transactivation reporter assay; metabolic labeling PNAS High 7604007
2003 Pim-1 serine/threonine kinase directly interacts with c-Myb via the Myb DNA-binding domain and phosphorylates this domain, providing a mechanism to regulate c-Myb protein activity. In vitro binding and kinase assay; co-immunoprecipitation Cell Cycle Medium 12734436
2000 p53 directly binds HSF3 and blocks the c-Myb–HSF3 interaction; p53 also stimulates proteasome-dependent degradation of c-Myb partly via Siah induction, suppressing c-Myb-activated HSF3 activation and HSP expression. Co-immunoprecipitation; proteasome inhibitor experiments; transactivation assay Journal of Biological Chemistry Medium 10747903
2008 Fbxw7 (F-box E3 ubiquitin ligase) targets c-Myb for NLK-induced proteasomal degradation; Fbxw7α binds c-Myb via its WD40 domain in a manner enhanced by NLK phosphorylation of c-Myb, induces c-Myb ubiquitination in vitro and in vivo; v-Myb is resistant to this degradation. In vitro ubiquitination assay; co-immunoprecipitation; siRNA knockdown; mutant analysis Journal of Biological Chemistry High 18765672
2005 TRAF7 binds the DNA-binding domain of c-Myb via WD40 repeats and promotes sumoylation of c-Myb at Lys-523 and Lys-499 (same sites as PIASy-induced sumoylation), sequestering sumoylated c-Myb in the cytoplasm and inhibiting its transactivation activity. Co-immunoprecipitation; sumoylation assay; subcellular fractionation; transactivation assay Molecular Biology of the Cell High 16162816
2004 TIF1β directly binds the c-Myb negative regulatory domain and recruits Ski, N-CoR, mSin3A, and histone deacetylase complex to negatively regulate c-Myb transactivation; Ski competes with CBP for c-Myb binding. NRD mutations in oncogenic v-Myb reduce corepressor binding. Co-immunoprecipitation; GST pull-down; transactivation assay; HDAC recruitment assay Journal of Biological Chemistry High 14761981
2001 BS69 (adenovirus E1A-associated protein) interacts directly with the C-terminal region of c-Myb and dose-dependently inhibits its transcriptional activity in animal cells; E1A 289R protein can relieve this BS69-mediated inhibition. Yeast two-hybrid; in vitro pull-down; transactivation reporter assay Oncogene Medium 11244510
2000 c-Myb directly activates the endogenous chromosomal c-myc gene at the transcriptional level in myeloid cells, and c-myc is a major transducer of c-Myb's proliferative signal; this was shown using a conditional MybER fusion in the presence of protein synthesis inhibitor. Conditional MybER activation; RT-PCR; protein synthesis inhibitor (cycloheximide) control; dominant-negative Myb in leukemia cells Molecular and Cellular Biology High 10688644
2009 c-Myb interaction with CBP/p300 via its transactivation domain is essential for myeloid transformation; single point mutations in the transactivation domain disrupting CBP/p300 binding abrogated transforming ability. Mutations in DNA-binding and NRD domains together also abolished transformation and CBP/p300 binding. Site-directed mutagenesis; myeloid cell transformation assay; primary hematopoietic cell assay; co-immunoprecipitation Molecular Cancer Research High 19737967
2007 miR-150 directly controls c-Myb protein levels in vivo in a dose-dependent manner and this regulation dramatically affects B and T lymphocyte development and response; c-Myb is a critical target of miR-150. Loss- and gain-of-function miR-150 targeting combined with conditional c-myb ablation in mice; in vivo genetic interaction Cell High 17923094
2010 c-Myb is recruited to the MLL histone methyltransferase complex via menin, contributes to H3K4 methylation, and regulates HOXA9 and MEIS1 expression; c-Myb silencing decreased global H3K4 methylation and reduced MLL and menin occupancy at the HOXA9 locus. Co-immunoprecipitation; ChIP; siRNA knockdown; MLL-ENL transformation assay Journal of Clinical Investigation High 20093773
2017 c-MYB protein is degraded via the proteasome upon mebendazole treatment through interference with the HSP70 chaperone system; this degradation inhibits AML cell colony formation and progression in vivo. Proteasome inhibitor rescue; chaperone interaction assay; in vivo xenotransplantation Leukemia Medium 29089643
2022 Withaferin A induces c-MYB protein ablation by disrupting HSP/HSC70 chaperone homeostasis via unfolded protein response; anti-AML activity is dependent on c-MYB modulation as demonstrated by partial reversal with a stabilized c-MYB mutant. Protein stability assay; proteasome/chaperone inhibition; stabilized mutant rescue; viability and colony assays Leukemia Medium 35368048
2011 Pdcd4 binds directly to the coding region of c-myb mRNA via its N-terminal RNA-binding domain and suppresses c-myb translation; N-terminal domain of Pdcd4 mediates preferential binding to the Pdcd4-responsive region of c-myb mRNA. RNA co-immunoprecipitation; in vitro translation suppression assay; deletion mutagenesis Oncogene Medium 21643008
2008 Pin1 isomerase binds c-Myb in a phosphorylation-dependent manner at S528 in the EVES motif and increases c-Myb transactivation activity in a manner dependent on Pin1 catalytic activity; physical interaction shown by co-IP in HL60 cells. Co-immunoprecipitation; transactivation reporter assay; point mutagenesis; mass spectrometry Biochimica et Biophysica Acta Medium 18359295
2000 c-Myb and GATA-1 mutually inhibit each other's transcriptional activity through competitive/exclusive binding to the shared coactivator CBP; tripartite c-Myb/GATA-1/CBP complex is not formed. Co-immunoprecipitation; transactivation reporter assay; competitive binding assay Oncogene Medium 10644988
2011 TIP60 histone acetyltransferase interacts with c-Myb via TIP60 acetyltransferase domain and c-Myb transactivation domain; TIP60 recruits HDAC1/HDAC2 to c-Myb and decreases c-Myb transcriptional activity; knockdown of Tip60 increases endogenous c-Myc expression. Co-immunoprecipitation; ChIP; reporter assay; siRNA knockdown Journal of Biological Chemistry Medium 22110127
2004 c-Myb is required at three distinct checkpoints during thymocyte development (DN3 transition, survival of preselection DP thymocytes, CD4 differentiation) as demonstrated by tissue-specific conditional deletion of c-myb at defined stages. Cre-lox tissue-specific conditional knockout; flow cytometric analysis of thymocyte subsets Nature Immunology High 15195090
2007 c-Myb directly regulates Gata3 gene expression and is required for upregulation of Gata3 following TCR selection signaling; loss of c-Myb blocks helper T cell differentiation. Gata3 was identified as a direct transcriptional target of c-Myb. Conditional knockout; gain-of-function transgene; ChIP; reporter assay; flow cytometry EMBO Journal High 17641686
2010 c-Myb primes DP thymocytes for iNKT lineage selection by simultaneously regulating CD1d expression, DP thymocyte half-life, and SLAMF1/SLAMF6/SAP expression. Conditional knockout; flow cytometry; gene expression analysis Nature Immunology High 20383148
2009 c-Myb is required for pro-B cell differentiation and intrinsic survival; c-Myb-deficient CD19+ pro-B cells show impaired IL-7Rα (CD127) and Ebf1 expression; exogenous Ebf1 can partially rescue B-lineage differentiation from c-Myb-deficient progenitors. Conditional (Mb1-Cre) knockout; retroviral rescue; flow cytometry; stromal cell culture Journal of Immunology High 19843942
2007 c-Myb is required for colonic crypt progenitor cell homeostasis; hypomorphic c-myb mutations reduce crypt size, impair progenitor proliferation via reduced Cyclin E1 expression, and tissue-specific deletion confirms requirement for normal crypt integrity and differentiation. Hypomorphic mutant mice; tissue-specific conditional knockout; in vivo proliferation markers; immunohistochemistry PNAS High 17360438
2008 c-Myb is required for smooth muscle cell (SMC) differentiation from embryonic stem cells; c-myb-/- ESCs fail to produce contracting SMCs and show deficient upregulation of myocardin and SMC-specific genes; c-myb-/- cells are also under-represented in SMC lineage of chimeric embryo aortas. c-myb-/- ESC differentiation; embryoid body assay; qRT-PCR; FACS; chimeric embryo analysis Circulation Research High 18187733
2005 c-Myb stability is regulated by a PI-3K/Akt/GSKIIIβ pathway; BCR/ABL-expressing cells show longer c-Myb half-life via this pathway. Leucine-zipper domain (residues 358–452) and lysine residues mediate c-Myb proteasomal degradation; degradation-resistant mutants show enhanced proliferative potential in hematopoietic cells. PI3K/Akt inhibitors; dominant-negative constructs; pulse-chase stability assay; colony formation assay Journal of Biological Chemistry Medium 15927960
2017 c-Myb D152V mutation disrupts histone binding of the third Myb repeat (R3) in the DNA-binding domain, impairing pioneer factor function and chromatin opening at specific sites (as shown by ATAC-seq), and specifically affects c-Myb's ability to regulate differentiation-associated genes. ATAC-seq; transcriptome analysis; histone-binding assay; site-directed mutagenesis Nucleic Acids Research High 28472346
2002 c-Myb cooperatively binds with Pax-5 to the RAG-2 promoter to activate its transcription in immature B cells; C-terminus of c-Myb mediates interaction with Pax-5; dominant-negative c-Myb suppresses RAG-2 promoter activity. Cotransfection reporter assay; EMSA; co-immunoprecipitation; dominant-negative mutant Blood Medium 11781241
2008 Alternative splicing generates multiple c-Myb protein isoforms (using exons 8A, 9A, 9B, 10A, 13A, 14A) with identical DNA-binding domains but distinct C-terminal domains; these isoforms show quantitative and qualitative differences in transcriptional activity and specificity; alternative splicing is enhanced in primary leukemia samples. RT-PCR quantitative splicing analysis; polysome association; transactivation reporter assay; microarray Molecular and Cellular Biology Medium 18195038
2010 The essential role of c-myb in definitive hematopoiesis is evolutionarily conserved in zebrafish; a missense mutation (I181N) in the DNA recognition helix of repeat 3 of the DBD causes complete failure of definitive hematopoiesis while sparing primitive hematopoiesis. ENU mutagenesis screen; loss-of-function genetic analysis in zebrafish; functional domain mapping PNAS High 20823231
1987 Differential expression of c-myb between pre-B and mature B lymphomas is mediated by a regulated block to transcription elongation in the first intron of the c-myb locus, correlated with changes in DNase I hypersensitivity (chromatin structure). Nuclear run-on transcription assay; DNase I hypersensitivity assay Science High 3498214
2011 ChIP-chip analysis identified >10,000 c-Myb-associated promoters in MCF-7 breast cancer cells including CXCR4, JUN, KLF4, NANOG, and MYC; estradiol stimulation triggers genome-wide c-Myb promoter association and target gene activation; c-Myb directly activates a CXCR4 reporter. ChIP-chip (whole genome promoter tiling array); reporter assay BMC Cancer Medium 21261996

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 A c-myb antisense oligodeoxynucleotide inhibits normal human hematopoiesis in vitro. Science (New York, N.Y.) 436 2461588
1986 Expression of the c-myb proto-oncogene during cellular proliferation. Nature 361 3511387
1996 CBP as a transcriptional coactivator of c-Myb. Genes & development 317 8598284
1987 Differential expression of c-myb mRNA in murine B lymphomas by a block to transcription elongation. Science (New York, N.Y.) 258 3498214
1989 G1/S transition in normal human T-lymphocytes requires the nuclear protein encoded by c-myb. Science (New York, N.Y.) 226 2665077
1986 Human c-myb protooncogene: nucleotide sequence of cDNA and organization of the genomic locus. Proceedings of the National Academy of Sciences of the United States of America 191 3540945
1994 Dominant interfering alleles define a role for c-Myb in T-cell development. Genes & development 166 7926766
1984 Amplification of the c-myb oncogene in a case of human acute myelogenous leukemia. Science (New York, N.Y.) 165 6585957
2004 Critical functions for c-Myb at three checkpoints during thymocyte development. Nature immunology 164 15195090
1996 The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb. Genes & development 153 8756344
1989 Trans-activation by the c-myb proto-oncogene. Nucleic acids research 149 2536148
1986 Two modes of c-myb activation in virus-induced mouse myeloid tumors. Molecular and cellular biology 144 3023843
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 131 10323859
2016 AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB. Science signaling 128 27601730
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
1984 Autoimmunity and increased c-myb transcription. Science (New York, N.Y.) 115 6494925
1986 Structure of the protein encoded by the chicken proto-oncogene c-myb. Molecular and cellular biology 109 3025608
1992 Carboxy-terminal elements of c-Myb negatively regulate transcriptional activation in cis and in trans. Genes & development 107 1340467
1989 Activation of c-myb by carboxy-terminal truncation: relationship to transformation of murine haemopoietic cells in vitro. The EMBO journal 107 2670562
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
1988 Rapid induction of B-cell lymphomas: insertional activation of c-myb by avian leukosis virus. Journal of virology 98 2831403
1988 Regulation of c-myb expression in human neuroblastoma cells during retinoic acid-induced differentiation. Molecular and cellular biology 97 3380093
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
2017 Targeting acute myeloid leukemia by drug-induced c-MYB degradation. Leukemia 90 29089643
2006 Coordination of erythropoiesis by the transcription factor c-Myb. Blood 90 16484593
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 Transcription regulation by murine B-myb is distinct from that by c-myb. Nucleic acids research 81 8382794
2003 Targeting c-Myb expression in human disease. Expert opinion on therapeutic targets 76 12667100
2000 Increased affinity of c-Myb for CREB-binding protein (CBP) after CBP-induced acetylation. The Journal of biological chemistry 76 11073948
2011 Identification and regulation of c-Myb target genes in MCF-7 cells. BMC cancer 75 21261996
1995 Modulation of c-Myb-induced transcription activation by a phosphorylation site near the negative regulatory domain. Proceedings of the National Academy of Sciences of the United States of America 75 7604007
2000 p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3. The Journal of biological chemistry 72 10747903
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
1990 Differentiation of mouse erythroleukemia cells enhanced by alternatively spliced c-myb mRNA. Science (New York, N.Y.) 69 2205003
1985 Activation of c-myb expression by phytohemagglutinin stimulation in normal human T lymphocytes. Molecular and cellular biology 68 3915538
2010 The transcription factor c-Myb primes CD4+CD8+ immature thymocytes for selection into the iNKT lineage. Nature immunology 66 20383148
2006 Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development. Blood 65 16597594
2017 miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb. Cell reports 64 28903040
2006 Transgene insertion in proximity to the c-myb gene disrupts erythroid-megakaryocytic lineage bifurcation. Molecular and cellular biology 63 16940183
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