Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.

Abstract

We have identified a human homolog of the Drosophila trithorax protein that is structurally altered by 11q23 translocations in acute leukemias. Human trithorax (HRX) is a predicted 431 kd protein containing two potential DNA-binding motifs consisting of zinc fingers conserved with the fly protein and nonconserved amino-terminal "AT hook" motifs related to the DNA-binding motifs in HMG proteins. 11q23 translocations disrupt the HRX gene between these two motifs, and in a t(11;19)-carrying cell line fusion transcripts are expressed from both derivative chromosomes. The more abundant derivative 11 transcript codes for a chimeric protein containing the AT hook motifs fused to a previously undescribed protein (ENL) from chromosome 19. These data suggest a novel role for a trithorax-homologous protein in multilineage human leukemias that may be mediated by DNA binding within the minor groove at AT-rich sites, implicated to play an important role in bacterial IHF-, yeast datin-, and mammalian HMG-mediated gene activation.

• Authors: D C Tkachuk, S Kohler, M L Cleary
• Journal: Cell (Cell) Vol. 71 Issue 4 Pg. 691-700 (Nov 13 1992) ISSN: 0092-8674 [Print] United States
• PMID: 1423624 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA-Binding Proteins
• Drosophila Proteins
• KMT2A protein, human
• Transcription Factors
• Trl protein, Drosophila
• Myeloid-Lymphoid Leukemia Protein
• Histone-Lysine N-Methyltransferase

Topics

• Acute Disease
• Amino Acid Sequence
• Animals
• Base Sequence
• Chromosomes, Human, Pair 11
• Chromosomes, Human, Pair 19
• DNA-Binding Proteins (chemistry, genetics)
• Drosophila (genetics)
• Drosophila Proteins
• Gene Expression Regulation, Leukemic (genetics)
• Histone-Lysine N-Methyltransferase
• Humans
• Leukemia (genetics)
• Molecular Sequence Data
• Myeloid-Lymphoid Leukemia Protein
• Proto-Oncogenes
• Sequence Homology, Nucleic Acid
• Transcription Factors
• Transcriptional Activation
• Translocation, Genetic (genetics)
• Zinc Fingers (genetics)