Abstract
The c-Myb transcription factor is a proto-oncoprotein whose latent transforming activity can be unmasked by truncation of either terminus. Because both ends of Myb are involved in negative regulation, we tested whether they could associate in a two-hybrid assay and identified a carboxy-terminal motif that interacts with the amino-terminal DNA-binding domain. The EVES motif is highly conserved in vertebrate c-Myb proteins and contains a known site of phosphorylation previously implicated in the negative regulation of c-Myb. Interestingly, a related EVES motif is present in p100, a ubiquitously expressed transcriptional coactivator found in diverse species. We show that p100 interacts with and influences the activity of c-Myb, implicating it in the regulation of c-Myb, differentiation, and cell growth. Our results suggest that Myb is regulated by a novel mechanism in which intramolecular interactions and conformational changes control the intermolecular associations among Myb, p100, and the transcriptional apparatus.
References
75
Referenced
136
10.1006/jmbi.1990.9999
{'key': '2021111418385921000_10.15.1858.2', 'first-page': '971', 'article-title': 'Characterization and expression of the Xenopus c-Myb homolog.', 'volume': '9', 'year': '1994', 'journal-title': 'Oncogene'}
/ Oncogene / Characterization and expression of the Xenopus c-Myb homolog. (1994){'key': '2021111418385921000_10.15.1858.3', 'first-page': '2259', 'article-title': 'c-Myb and v-Myb are differentially phosphorylated by p42mapk in vitro.', 'volume': '8', 'year': '1993', 'journal-title': 'Oncogene'}
/ Oncogene / c-Myb and v-Myb are differentially phosphorylated by p42mapk in vitro. (1993)10.1073/pnas.92.14.6429
{'key': '2021111418385921000_10.15.1858.5', 'first-page': '59', 'article-title': 'Only late, nonmitotic stages of granulocyte differentiation in 32Dcl3 cells are blocked by ectopic expression of murine c-myb and its truncated forms.', 'volume': '6', 'year': '1995', 'journal-title': 'Cell Growth Differ.'}
/ Cell Growth Differ. / Only late, nonmitotic stages of granulocyte differentiation in 32Dcl3 cells are blocked by ectopic expression of murine c-myb and its truncated forms. (1995){'key': '2021111418385921000_10.15.1858.6', 'first-page': '35', 'article-title': 'Molecular themes in oncogenesis.', 'volume': '64', 'year': '1991', 'journal-title': 'Cell'}
/ Cell / Molecular themes in oncogenesis. (1991)10.1093/nar/19.7.1533
10.1016/0092-8674(85)90246-6
10.1002/j.1460-2075.1993.tb05852.x
/ EMBO J. / Synergistic activation of the chicken mim-1 gene by v-myb and C/EBP transcription factors. (1993){'key': '2021111418385921000_10.15.1858.10', 'first-page': '4423', 'article-title': 'Differential Transcriptional Activation by v-Myb and c-Myb in animal cells and Saccharomyces cervisiae.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Differential Transcriptional Activation by v-Myb and c-Myb in animal cells and Saccharomyces cervisiae. (1993){'key': '2021111418385921000_10.15.1858.11', 'first-page': '1884', 'article-title': 'Constitutive expression of a c-myb cDNA blocks friend murine erythroleukemia cell differentiation.', 'volume': '8', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Constitutive expression of a c-myb cDNA blocks friend murine erythroleukemia cell differentiation. (1988)10.1101/gad.10.5.528
{'key': '2021111418385921000_10.15.1858.13', 'first-page': '7334', 'article-title': 'Oncogenic truncation of the first repeat of c-Myb decreases DNA binding in vitro and in vivo.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Oncogenic truncation of the first repeat of c-Myb decreases DNA binding in vitro and in vivo. (1993)10.1128/jvi.69.4.2515-2524.1995
/ J. Virol. / Mutations in the DNA-binding and transcriptional activation domains of v-Myb cooperate in transformation. (1995)10.1101/gad.6.12b.2524
10.1006/viro.1995.1177
10.1128/MCB.15.10.5820
/ Mol. Cell. Biol. / Correlation of two-hybrid affinity data with in vitro measurements. (1995){'key': '2021111418385921000_10.15.1858.18', 'first-page': '305', 'article-title': 'Detection of proteins that bind to the leucine zipper motif of c-Myb.', 'volume': '9', 'year': '1994', 'journal-title': 'Oncogene'}
/ Oncogene / Detection of proteins that bind to the leucine zipper motif of c-Myb. (1994){'key': '2021111418385921000_10.15.1858.19', 'first-page': '1631', 'article-title': 'Enforced expression of full length c-Myb leads to density-dependent transformation of murine haemopoietic cells.', 'volume': '11', 'year': '1995', 'journal-title': 'Oncogene'}
/ Oncogene / Enforced expression of full length c-Myb leads to density-dependent transformation of murine haemopoietic cells. (1995)10.1038/340245a0
10.1038/342134a0
10.1002/j.1460-2075.1993.tb05778.x
/ EMBO J. / Influence of the v-Myb transactivation domain on the oncoprotein's transformation specificity. (1993)10.1007/BF01977350
{'key': '2021111418385921000_10.15.1858.24', 'first-page': '265', 'article-title': 'Determinants of sequence-specific DNA-binding by p48v-myb.', 'volume': '6', 'year': '1991', 'journal-title': 'Oncogene'}
/ Oncogene / Determinants of sequence-specific DNA-binding by p48v-myb. (1991){'key': '2021111418385921000_10.15.1858.25', 'first-page': '3677', 'article-title': 'Structure of the protein encoded by the chicken proto-oncogene c-myb.', 'volume': '6', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Structure of the protein encoded by the chicken proto-oncogene c-myb. (1986)10.1182/blood.V77.1.149.149
/ Blood / Expression of c-myb and B-myb, but not A-myb, correlates with proliferation in human hematopoietic cells. (1991){'key': '2021111418385921000_10.15.1858.27', 'first-page': '3006', 'article-title': 'Fused protein domains inhibit DNA binding by LexA.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Fused protein domains inhibit DNA binding by LexA. (1992)10.1002/j.1460-2075.1989.tb03571.x
/ EMBO J. / Activation of c-myb by carboxy-terminal truncation: Relationship to transformation of murine haemopoietic cells in vitro. (1989)-
Gonda, T.J., Ramsay, R.G. and Johnson. G.R. 1989b. Murine myeloid cell lines derived by in vitro infection with recombinant c-myb retroviruses express myb from rearranged vector proviruses. EMBO J. 8: 1767-1175.
(
10.1002/j.1460-2075.1989.tb03570.x
) {'key': '2021111418385921000_10.15.1858.30', 'first-page': '3987', 'article-title': 'Protein truncation is required for the activation of the c-myb proto-oncogene.', 'volume': '11', 'year': '1991', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Protein truncation is required for the activation of the c-myb proto-oncogene. (1991)10.1128/MCB.15.7.3618
/ Mol. Cell. Biol. / Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA-binding protein and TFIIB. (1995)10.1016/0092-8674(93)90498-F
10.1002/j.1460-2075.1990.tb08092.x
/ EMBO J. / Characterization of the sequence-specific interaction of mouse c-myb protein with DNA. (1990){'key': '2021111418385921000_10.15.1858.34', 'first-page': '1549', 'article-title': 'Transformation by carboxyl-deleted Myb reflects increased transactivating capacity and disruption of a negative regulatory domain.', 'volume': '6', 'year': '1991', 'journal-title': 'Oncogene'}
/ Oncogene / Transformation by carboxyl-deleted Myb reflects increased transactivating capacity and disruption of a negative regulatory domain. (1991){'key': '2021111418385921000_10.15.1858.35', 'first-page': '2285', 'article-title': 'trans-Activation of gene expression by v-myb.', 'volume': '10', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / trans-Activation of gene expression by v-myb. (1990)10.1016/0092-8674(90)90424-D
10.1128/MCB.16.5.2065
/ Mol. Cell. Biol. / Characterization of the cooperative function of inhibitory sequences in Ets-1. (1996)10.1073/pnas.89.7.3088
10.1002/j.1460-2075.1993.tb05777.x
/ EMBO J. / The NF-M transcription factor is related to C/EBPβ and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells. (1993){'key': '2021111418385921000_10.15.1858.40', 'first-page': '2591', 'article-title': 'Transformation by v-myb correlates with trans-activation of gene expression.', 'volume': '10', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Transformation by v-myb correlates with trans-activation of gene expression. (1990)10.1038/344517a0
{'key': '2021111418385921000_10.15.1858.42', 'first-page': '705', 'article-title': 'Differentiation of mouse erythroleukemia cells is blocked by late up-regulation of a c-myb transgene.', 'volume': '10', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Differentiation of mouse erythroleukemia cells is blocked by late up-regulation of a c-myb transgene. (1990)10.1074/jbc.270.16.9384
10.1128/jvi.66.10.6035-6044.1992
/ J. Virol. / New sites of proviral integration associated with murine promonocytic leukemias and evidence for alternate modes of c-myb activation. (1992)10.1073/pnas.90.4.1619
10.1128/MCB.15.11.5975
/ Mol. Cell. Biol. / YY1 facilitates the association of serum response factor with the c-fos serum response element. (1995)10.1016/0092-8674(89)90767-8
10.1101/gad.7.5.749
-
Ness, S.A. 1996. The Myb Oncoprotein: Regulating a regulator. Biochem. Biophys. Acta Rev. Cancer. (in press).
(
10.1016/S0304-419X(96)00027-3
) 10.1093/nar/16.23.11075
10.1016/S0021-9258(20)80628-0
/ J. Biol. Chem. / Negative auto-regulation of c-Myb activity by homodimer formation through the leucine zipper. (1993)10.1128/MCB.15.11.5966
/ Mol. Cell. Biol. / Casein kinase II phosphorylation site mutations in c-Myb affect DNA binding and transcriptional cooperativity with NF-M. (1995)10.1002/j.1460-2075.1996.tb00637.x
/ EMBO J. / Interaction of the co-activator CBP with Myb proteins: Effects on the Myb-specific transcription and on the cooperativity with NF-M. (1996){'key': '2021111418385921000_10.15.1858.54', 'first-page': '201', 'article-title': 'Solution structures of Myb DNA-binding domain and its complex with DNA.', 'volume': '29', 'year': '1993', 'journal-title': 'Nucleic Acids Symp. Ser.'}
/ Nucleic Acids Symp. Ser. / Solution structures of Myb DNA-binding domain and its complex with DNA. (1993)10.1016/0092-8674(94)90549-5
10.1016/0955-0674(93)90016-J
10.1126/science.7569926
10.1016/0959-437X(94)90129-Q
{'key': '2021111418385921000_10.15.1858.59', 'first-page': '1815', 'article-title': 'Increase in specific DNA binding by carboxyl truncation suggests a mechanism for activation of Myb.', 'volume': '6', 'year': '1991', 'journal-title': 'Oncogene'}
/ Oncogene / Increase in specific DNA binding by carboxyl truncation suggests a mechanism for activation of Myb. (1991)10.1074/jbc.270.50.29976
10.1073/pnas.86.15.5758
{'key': '2021111418385921000_10.15.1858.62', 'first-page': '2493', 'article-title': 'Deregulated c-myb disrupts interleukin-6 or leukemia inhibitory factor-induced myeloid differentiation prior to c-myc: Role in leukemogenesis.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Deregulated c-myb disrupts interleukin-6 or leukemia inhibitory factor-induced myeloid differentiation prior to c-myc: Role in leukemogenesis. (1992)10.1126/science.6093260
{'key': '2021111418385921000_10.15.1858.64', 'first-page': '380', 'article-title': 'Two modes of c-myb activation in virus-induced mouse myeloid tumors.', 'volume': '6', 'year': '1986', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Two modes of c-myb activation in virus-induced mouse myeloid tumors. (1986){'key': '2021111418385921000_10.15.1858.65', 'first-page': '1931', 'article-title': 'Xenopus A-myb is expressed during early spermatogenesis.', 'volume': '8', 'year': '1993', 'journal-title': 'Oncogene'}
/ Oncogene / Xenopus A-myb is expressed during early spermatogenesis. (1993){'key': '2021111418385921000_10.15.1858.66', 'first-page': '237', 'article-title': 'c-Myb prevents TPA-induced differentiation and cell death in v-Myb transformed monoblasts.', 'volume': '9', 'year': '1994', 'journal-title': 'Oncogene'}
/ Oncogene / c-Myb prevents TPA-induced differentiation and cell death in v-Myb transformed monoblasts. (1994)10.1073/pnas.85.23.8900
10.1128/MCB.15.9.4735
/ Mol. Cell. Biol. / The Epstein-Barr virus nuclear protein 2 acidic domain forms a complex with a novel cellular coactivator that can interact with TFIIE. (1995)10.1002/j.1460-2075.1994.tb06945.x
/ EMBO J. / Mouse A-myb encodes a trans-activator and is expressed in mitotically active cells of the developing central nervous system, adult testis and B lymphocytes. (1994)10.1073/pnas.92.8.3132
10.1210/edrv-14-4-459
10.1093/nar/22.13.2466
10.1016/0092-8674(89)90405-4
10.1016/0167-4781(91)90128-9
/ Biochim. Biophys. Acta / Constitutive expression of exogenous c-myb gene causes maturation block in monocyte-macrophage differentiation. (1991)10.1016/0092-8674(93)90662-A
Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 9:54 p.m.) |
Indexed | 1 year, 1 month ago (July 17, 2024, 5:40 a.m.) |
Issued | 29 years, 1 month ago (Aug. 1, 1996) |
Published | 29 years, 1 month ago (Aug. 1, 1996) |
Published Online | 29 years, 1 month ago (Aug. 1, 1996) |
Published Print | 29 years, 1 month ago (Aug. 1, 1996) |
@article{Dash_1996, title={The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb.}, volume={10}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.10.15.1858}, DOI={10.1101/gad.10.15.1858}, number={15}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Dash, A B and Orrico, F C and Ness, S A}, year={1996}, month=aug, pages={1858–1869} }