|
|
Blood, 15 April 2004, Vol. 103, No. 8, pp. 3200-3207.
Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-07-2188.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Molecular basis for a dominant inactivation of RUNX1/AML1 by the leukemogenic inversion 16 chimera
Gang Huang,
Katsuya Shigesada,
Hee-Jun Wee,
P. Paul Liu,
Motomi Osato, and
Yoshiaki Ito
From the Institute for Virus Research, Kyoto University, Kyoto, Japan; Institute of Molecular and Cell Biology, Oncology Research Institute, National University of Singapore, Singapore; and National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
The Runt domain transcription factor, PEBP2/CBF, is a heterodimer composed of 2 subunits. The DNA-binding  subunit, or RUNX protein, interacts with a partner PEBP2 /CBF through the evolutionarily conserved Runt domain. Each of the genes encoding RUNX1 and PEBP2/CBF is frequently involved in acute myeloid leukemia. The chimeric protein, CBF(PEBP2)/SMMHC, is generated as a result of inversion of chromosome 16 in such a way to retain the heterodimerization domain of PEBP2 at the amino-terminal side fused to the C-terminal coiled-coil region of smooth muscle myosin heavy chain (SMMHC). Here we show that, in the chimeric protein, the second heterodimerization domain is created by the fusion junction, enabling the chimeric protein to interact with RUNX1 at far greater affinity than PEBP2 and inactivate the RUNX1/AML1 function. To explain why and how heterozygous CBFB/MYH11 can inactivate homozygous RUNX1 near to completion, we propose a new model for this chimeric protein that consists of a Y-shaped dimer with unpaired N-terminal halves followed by a coiled-coil for the C-terminal region. (Blood. 2004;103:3200-3207)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Yokomizo, K. Hasegawa, H. Ishitobi, M. Osato, M. Ema, Y. Ito, M. Yamamoto, and S. Takahashi
Runx1 is involved in primitive erythropoiesis in the mouse
Blood,
April 15, 2008;
111(8):
4075 - 4080.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-G. Kim, K. Kojima, C. S. Swindle, C. V. Cotta, Y. Huo, V. Reddy, and C. A. Klug
FLT3-ITD cooperates with inv(16) to promote progression to acute myeloid leukemia
Blood,
February 1, 2008;
111(3):
1567 - 1574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Markus, M. T. Garin, J. Bies, N. Galili, A. Raza, M. J. Thirman, M. M. Le Beau, J. D. Rowley, P. P. Liu, and L. Wolff
Methylation-Independent Silencing of the Tumor Suppressor INK4b (p15) by CBF{beta}-SMMHC in Acute Myelogenous Leukemia with inv(16)
Cancer Res.,
February 1, 2007;
67(3):
992 - 1000.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
