Article

Isolation and characterization of a pufferfish MLL (mixed lineage leukemia)-like gene (fMll) reveals evolutionary conservation in vertebrate genes related to Drosophila trithorax.

The Leukaemia Research Fund Centre at The Institute of Cancer Research, Chester Beatty Laboratories, London, UK.
Oncogene (impact factor: 6.37). 07/1998; 16(25):3233-41. DOI:10.1038/sj.onc.1201873
Source: PubMed

ABSTRACT The MLL gene is interrupted and fused to a number of partner genes as a result of chromosomal translocations in human leukemias. MLL is a very large protein with a unique domain structure and large regions of homology to Drosophila trx. To define the key structural and functional domains of the MLL protein in vertebrates, we have cloned the genomic region encoding an MLL-like gene in the compact model vertebrate genome of Fugu rubripes. While the similarity between the mouse and human MLL proteins is very high, a lower overall similarity is present between the Fugu and mammalian proteins. Several new highly conserved regions were identified in the portion of the protein included in the MLL leukemia-associated fusion proteins. The conserved nature of regions of similarity between vertebrate forms of MLL and the Drosophila TRX proteins, as well as other domains previously suggested to have a functional role in MLL (including the AT hooks and the DNA methyltransferase domain), was also observed. Therefore, strong evolutionary constraints limited sequence divergence within these domains. The information derived from this comparative analysis will form the basis for the functional study of the MLL protein, particularly as it relates to human leukemogenesis.

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Keywords

chromosomal translocations
 
compact model vertebrate genome
 
comparative analysis
 
DNA methyltransferase domain
 
Drosophila trx
 
Drosophila TRX proteins
 
functional role
 
functional study
 
genomic region encoding
 
human leukemogenesis
 
human MLL proteins
 
key structural
 
large regions
 
MLL gene
 
MLL leukemia-associated fusion proteins
 
MLL protein
 
MLL-like gene
 
partner genes
 
regions
 
unique domain structure
 

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