Characterization and chromosomal localization of the human proto-oncogene BMI-1

Abstract

The proto-oncogene bml-1 is frequently activated by Moloney murine leukemia proviral insertions in Eμ-mcy transgenic mice^1,2 Using a mouse bmi-1 cDNA probe a transcript of 3.3 kb was detected on Northern blots of human Burkitts lymphoma cell lines. We have Isolated and sequenced cDNA clones from a human erythroleukemia cell line (K562) derived cDNA library, using different mouse bml-l cDNA fragments as a probe. Analysis of genomic BMI-1 sequences reveals a gene structure which is very similar to that of the mouse, consisting of at least 10 exons. The human cDNA is 3203 bp in length and shows 86% identify to the mouse nucleotide sequence. The open reading frame encodes a protein of 326 amino acids which shares 98% Identity to the amino acid sequence of mouse bmi-1 protein. In vitro translation experiments show that human cDNA derived RNA translates into a protein with a mobility of 44–46 kD on SDS polyacrylamide gels. Fluorescence In situ hybridization (FISH) on metaphase chromosome spreads located the human BMI-1 gene to the short arm of chromosome 10 (10p13), a region known to be involved in translocations in various leukemias.