THE LEUKEMIA-ASSOCIATED-PROTEIN (LAP) DOMAIN, A CYSTEINE-RICH MOTIF, IS PRESENT IN A WIDE-RANGE OF PROTEINS, INCLUDING MLL, AF10, AND MLLT6PROTEINS

We have identified and further characterized a Caenorhabditis elegans gene, CEZF, that encodes a protein with substantial homology to the zi nc finger and leucine zipper motifs of the human gene products AF10, M LLT6, 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 fro m previously described zinc finger motifs, sequence homology searches were done, Twenty-five other proteins with a similar motif were identi fied, Because the functional domain of this motif is potentially disru pted in leukemia-associated chromosomal translocations, we propose the name of leukemia-associated protein (LAP) finger. On the basis of the se comparisons, the LAP domain consensus sequence is (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 mo tif binds zinc, is the important DNA-binding domain in this group of r egulatory proteins, and may be involved in leukemogenesis.