Linked Life Data

12816872

Source:http://linkedlifedata.com/resource/pubmed/id/12816872

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-10-21
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3323-32
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12816872-Acute Disease, pubmed-meshheading:12816872-Animals, pubmed-meshheading:12816872-Base Sequence, pubmed-meshheading:12816872-Cell Differentiation, pubmed-meshheading:12816872-Cell Line, Tumor, pubmed-meshheading:12816872-Chromosomes, Human, Pair 1, pubmed-meshheading:12816872-Chromosomes, Human, Pair 3, pubmed-meshheading:12816872-Consensus Sequence, pubmed-meshheading:12816872-DNA-Binding Proteins, pubmed-meshheading:12816872-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:12816872-Humans, pubmed-meshheading:12816872-Leukemia, Myeloid, pubmed-meshheading:12816872-Mice, pubmed-meshheading:12816872-Molecular Sequence Data, pubmed-meshheading:12816872-Myeloid Cells, pubmed-meshheading:12816872-Protein Structure, Tertiary, pubmed-meshheading:12816872-Transcription Factors, pubmed-meshheading:12816872-Transcription Initiation Site, pubmed-meshheading:12816872-Transcriptional Activation, pubmed-meshheading:12816872-Translocation, Genetic
pubmed:year
2003
pubmed:articleTitle
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.
pubmed:affiliation
Department of Biochemistry, Miyazaki Medical College, Kiyotake, Miyazaki, 889-1692, Japan. kmorishi@post.miyazaki-med.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't