|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 December 2000, Vol. 96, No. 12, pp. 3939-3947
NEOPLASIA
AML-1/ETO fusion protein is a dominant negative
inhibitor of transcriptional repression by the promyelocytic leukemia
zinc finger protein
Ari Melnick,
Graeme W. Carlile,
Melanie J. McConnell,
Adam Polinger,
Scott W. Hiebert, and
Jonathan D. Licht
From the Department of Medicine, The Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY;
and the Department of Biochemistry, Vanderbilt University School of
Medicine, Nashville, TN.
The AML-1/ETO fusion protein, created by the (8;21) translocation
in M2-type acute myelogenous leukemia (AML), is a dominant repressive
form of AML-1. This effect is due to the ability of the ETO portion of
the protein to recruit co-repressors to promoters of AML-1 target
genes. The t(11;17)(q21;q23)-associated acute promyelocytic leukemia
creates the promyelocytic leukemia zinc finger PLZFt/RAR fusion
protein and, in a similar manner, inhibits RAR target gene
expression and myeloid differentiation. PLZF is expressed in
hematopoietic progenitors and functions as a growth suppressor by
repressing cyclin A2 and other targets. ETO is a corepressor for PLZF
and potentiates transcriptional repression by linking PLZF to a histone
deacetylase-containing complex. In transiently transfected cells and in
a cell line derived from a patient with t(8;21) leukemia, PLZF and
AML-1/ETO formed a tight complex. In transient assays, AML-1/ETO
blocked transcriptional repression by PLZF, even at substoichiometric
levels relative to PLZF. This effect was dependent on the presence of
the ETO zinc finger domain, which recruits corepressors, and could not be rescued by overexpression of co-repressors that normally enhance PLZF repression. AML-1/ETO also excluded PLZF from the nuclear matrix
and reduced its ability to bind to its cognate DNA-binding site.
Finally, ETO interacted with PLZF/RAR and enhanced its ability to
repress through the RARE. These data show a link in the transcriptional
pathways of M2 and M3 leukemia.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. C. Moore, J. M. Amann, C. S. Williams, E. Tahinci, T. E. Farmer, J. A. Martinez, G. Yang, K. S. Luce, E. Lee, and S. W. Hiebert
Myeloid Translocation Gene Family Members Associate with T-Cell Factors (TCFs) and Influence TCF-Dependent Transcription
Mol. Cell. Biol.,
February 1, 2008;
28(3):
977 - 987.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bug, K. Schwarz, C. Schoch, M. Kampfmann, R. Henschler, D. Hoelzer, O. G. Ottmann, and M. Ruthardt
Effect of histone deacetylase inhibitor valproic acid on progenitor cells of acute myeloid leukemia
Haematologica,
April 1, 2007;
92(4):
542 - 545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-H. Ma, H. Liu, H. Xiong, B. Chen, X.-W. Zhang, Y.-Y. Wang, H.-Y. Le, Q.-H. Huang, Q.-H. Zhang, B.-L. Li, et al.
Aberrant transcriptional regulation of the MLL fusion partner EEN by AML1-ETO and its implication in leukemogenesis
Blood,
January 15, 2007;
109(2):
769 - 777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Choi, K. E. Elagib, L. L. Delehanty, and A. N. Goldfarb
Erythroid Inhibition by the Leukemic Fusion AML1-ETO Is Associated with Impaired Acetylation of the Major Erythroid Transcription Factor GATA-1.
Cancer Res.,
March 15, 2006;
66(6):
2990 - 2996.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Melnick, K. Adelson, and J. D. Licht
The Theoretical Basis of Transcriptional Therapy of Cancer: Can It Be Put Into Practice?
J. Clin. Oncol.,
June 10, 2005;
23(17):
3957 - 3970.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Liu, T. Shen, L. Huynh, M. I. Klisovic, L. J. Rush, J. L. Ford, J. Yu, B. Becknell, Y. Li, C. Liu, et al.
Interplay of RUNX1/MTG8 and DNA Methyltransferase 1 in Acute Myeloid Leukemia
Cancer Res.,
February 15, 2005;
65(4):
1277 - 1284.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yan, S. A. Burel, L. F. Peterson, E. Kanbe, H. Iwasaki, A. Boyapati, R. Hines, K. Akashi, and D.-E. Zhang
From the Cover: Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development
PNAS,
December 7, 2004;
101(49):
17186 - 17191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Platanias
SMRT interactions, repression, and Flt3-ITD
Blood,
June 15, 2004;
103(12):
4382 - 4382.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Takahashi, M. J. McConnell, H. Harigae, M. Kaku, T. Sasaki, A. M. Melnick, and J. D. Licht
The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT
Blood,
June 15, 2004;
103(12):
4650 - 4658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Muller-Tidow, B. Steffen, T. Cauvet, L. Tickenbrock, P. Ji, S. Diederichs, B. Sargin, G. Kohler, M. Stelljes, E. Puccetti, et al.
Translocation Products in Acute Myeloid Leukemia Activate the Wnt Signaling Pathway in Hematopoietic Cells
Mol. Cell. Biol.,
April 1, 2004;
24(7):
2890 - 2904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Chevallier, C. M. Corcoran, C. Lennon, E. Hyjek, A. Chadburn, V. J. Bardwell, J. D. Licht, and A. Melnick
ETO protein of t(8;21) AML is a corepressor for Bcl-6 B-cell lymphoma oncoprotein
Blood,
February 15, 2004;
103(4):
1454 - 1463.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F.-Q. Li, R. E. Person, K.-I. Takemaru, K. Williams, K. Meade-White, A. H. Ozsahin, T. Gungor, R. T. Moon, and M. Horwitz
Lymphoid Enhancer Factor-1 Links Two Hereditary Leukemia Syndromes through Core-binding Factor {alpha} Regulation of ELA2
J. Biol. Chem.,
January 23, 2004;
279(4):
2873 - 2884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Espinosa, J. Ingles-Esteve, A. Robert-Moreno, and A. Bigas
Ikappa Balpha and p65 Regulate the Cytoplasmic Shuttling of Nuclear Corepressors: Cross-talk between Notch and NFkappa B Pathways
Mol. Biol. Cell,
February 1, 2003;
14(2):
491 - 502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. G. Kroll
Molecular Rearrangements and Morphology in Thyroid Cancer
Am. J. Pathol.,
June 1, 2002;
160(6):
1941 - 1944.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Hug, S. Y. D. Lee, E. L. Kinsler, J. Zhang, and M. A. Lazar
Cooperative Function of Aml1-ETO Corepressor Recruitment Domains in the Expansion of Primary Bone Marrow Cells
Cancer Res.,
May 1, 2002;
62(10):
2906 - 2912.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
