|
|
Blood, 1 November 2003, Vol. 102, No. 9, pp. 3323-3332.
Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2002-12-3944.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF–induced myeloid differentiation
Ichiro Nishikata,
Hidenori Sasaki,
Mutsunori Iga,
Yoko Tateno,
Suzuko Imayoshi,
Norio Asou,
Takuro Nakamura, and
Kazuhiro Morishita
From the Department of Biochemistry and Second Department of Internal Medicine, Miyazaki Medical College, Japan; Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan; and The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
We have identified a novel gene MEL1 (MDS1/EVI1-like gene 1) encoding a zinc finger protein near the breakpoint of t(1; 3)(p36;q21)-positive human acute myeloid leukemia (AML) cells. Here, we studied the structure, expression pattern, and function of MEL1 in leukemia cells. In this study, we have identified 3 transcription start sites, 1 in exon 1 and 2 in exon 2, and 2 kinds of translation products, 170 kDa (MEL1) and 150 kDa (MEL1S). Notably, the 150-kDa band of MEL1S was detected mainly in the t(1;3)(p36;q21)-positive AML cells. By immunoblot analysis and proteolytic mapping, it is suggested that the 150-kDa band of MEL1S in the leukemia cells is translated from the internal initiation codon ATG597 in exon 4 and is mostly lacking the amino-terminal PR domain of MEL1. By the cyclic amplification and selection of targets (CASTing) method for identifying consensus sequences, it was shown that the consensus sequences of MEL1 were included in 2 different consensus sequences for DNA-binding domain 1 and 2 (D1-CONS and D2-CONS) of EVI1. In reporter gene assays, MEL1S activated transcription via binding to D2-CONS; however, the fusion of MEL1 or MEL1S to GAL4 DNA-binding domain (DBD) made them GAL4 binding site–dependent transcriptional repressors. Moreover, overexpression of MEL1S blocked granulocytic differentiation induced by granulocyte colony-stimulating factor (G-CSF) in interleukin-3 (IL-3)–dependent murine myeloid L-G3 cells, while MEL1 could not block the differentiation. Thus, it is likely that overexpression of the zinc finger protein lacking the PR domain (EVI1 and MEL1S) in the leukemia cells is one of the causative factors in the pathogenesis of myeloid leukemia.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Kajimura, P. Seale, T. Tomaru, H. Erdjument-Bromage, M. P. Cooper, J. L. Ruas, S. Chin, P. Tempst, M. A. Lazar, and B. M. Spiegelman
Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex
Genes & Dev.,
May 15, 2008;
22(10):
1397 - 1409.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Duan, R. E. Person, H.-H. Lee, S. Huang, J. Donadieu, R. Badolato, H. L. Grimes, T. Papayannopoulou, and M. S. Horwitz
Epigenetic Regulation of Protein-Coding and MicroRNA Genes by the Gfi1-Interacting Tumor Suppressor PRDM5
Mol. Cell. Biol.,
October 1, 2007;
27(19):
6889 - 6902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Miremadi, M. Z. Oestergaard, P. D.P. Pharoah, and C. Caldas
Cancer genetics of epigenetic genes
Hum. Mol. Genet.,
April 15, 2007;
16(R1):
R28 - R49.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Du, N. A. Jenkins, and N. G. Copeland
Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells
Blood,
December 1, 2005;
106(12):
3932 - 3939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Buonamici, D. Li, F. M. Mikhail, A. Sassano, L. C. Platanias, O. Colamonici, J. Anastasi, and G. Nucifora
EVI1 Abrogates Interferon-{alpha} Response by Selectively Blocking PML Induction
J. Biol. Chem.,
January 7, 2005;
280(1):
428 - 436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yoshida, K. Nosaka, J.-i. Yasunaga, I. Nishikata, K. Morishita, and M. Matsuoka
Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells
Blood,
April 1, 2004;
103(7):
2753 - 2760.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
