THE LEUKEMIA-ASSOCIATED-PROTEIN (LAP) DOMAIN, A CYSTEINE-RICH MOTIF, IS PRESENT IN A WIDE-RANGE OF PROTEINS, INCLUDING MLL, AF10, AND MLLT6 PROTEINS

We have identified and further characterized a Caenorhabditis elegans gene, CEZF, that encodes a protein with substantial homology to the zinc finger and leucine zipper motifs of the human gene products AF10, MLLT6, and BR140. The first part of the zinc finger region of CEZF has strong similarity to the corresponding regions of AF10 (66%) and MLLT6 (64%) at the cDNA level, As this region is structurally different from previously described zinc finger motifs, sequence homology searches were done, Twenty-five other proteins with a similar motif were identified, Because the functional domain of this motif is potentially disrupted in leukemia-associated chromosomal translocations, we propose the name of leukemia-associated protein (LAP) finger. On the basis of these comparisons, the LAP domain consensus sequence is Cys(1)-Xaa(1-2)-Cys(2)-Xaa(9-21)-Cys(3)-Xaa(2-4)-Cys(4)-Xaa(4-5)-His(5)-Xaa(2)-Cys(6)-Xaa(12-46)-Cys(7)-Xaa(2)-Cys(8), where subscripted numbers represent the number of amino acid residues, We review the evidence that this motif binds zinc, is the important DNA-binding domain in this group of regulatory proteins, and may be involved in leukemogenesis.