Alternative titles; symbols
HGNC Approved Gene Symbol: MLLT6
Cytogenetic location: 17q12 Genomic coordinates (GRCh38) : 17:38,705,273-38,729,795 (from NCBI)
Chromosome translocations involving the MLL (ALL1) gene (159555) on chromosome 11q23 are associated with approximately 10% of patients with acute lymphoblastic leukemia (ALL) and more than 5% of patients with acute myeloid leukemia (AML). Leukemia associated with 11q23 abnormalities tend to show expression of both lymphoid and myeloid markers (hence, 'mixed-lineage leukemia'), massive cell burden, and poor prognosis (see 159555). Prasad et al. (1994) cloned and characterized the AF17 gene as a translocation partner of MLL in the rare translocation t(11;17)(q23;q21). The AF17 gene encodes a protein of 1,093 amino acids, containing a leucine-zipper dimerization motif located 3-prime of the fusion point and a cysteine-rich domain at the N terminus. The latter can be arranged in 3 zinc fingers and shows homology to a domain within the protein Br140 (602410); see Thompson et al. (1994). AF17 was found to contain stretches of amino acids previously associated with domains involved in transcriptional repression or activation.
Based on features of AF17 and of the proteins encoded by the other partner genes of ALL1 that had been analyzed and in conjunction with other studies, Prasad et al. (1994) proposed a model in which ALL1 rearrangements result in loss of function of that gene. In this model, the partner polypeptide, such as that encoded by AF17, plays an accessory role either by repressing activity of the truncated ALL1 protein or by blocking the function of the normal protein presumably present in leukemic cells.
Focusing on skin development and oncogenic (Hras-G12V (190020.0001)-induced) hyperplasia, Beronja et al. (2013) carried out genomewide RNA interference-mediated screens in mice and uncovered theretofore unknown as well as anticipated regulators of embryonic epidermal growth. Among the top oncogenic screen hits were Mllt6 and the Wnt effector beta-catenin (116806), which maintain Hras-G12V-dependent hyperproliferation. Beronja et al. (2013) also exposed beta-catenin as an unanticipated antagonist of normal epidermal growth, functioning through Wnt-independent intercellular adhesion.
Prasad et al. (1994) identified the AF17 gene on chromosome 17q21.
Beronja, S., Janki, P., Heller, E., Lien, W.-H., Keyes, B. E., Oshimori, N., Fuchs, E. RNAi screens in mice identify physiological regulators of oncogenic growth. Nature 501: 185-190, 2013. [PubMed: 23945586] [Full Text: https://doi.org/10.1038/nature12464]
Prasad, R., Leshkowitz, D., Gu, Y., Alder, H., Nakamura, T., Saito, H., Huebner, K., Berger, R., Croce, C. M., Canaani, E. Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia. Proc. Nat. Acad. Sci. 91: 8107-8111, 1994. [PubMed: 8058765] [Full Text: https://doi.org/10.1073/pnas.91.17.8107]
Thompson, K. A., Wang, B., Argraves, W. S., Giancotti, F. G., Schranck, D. P., Ruoslahti, E. BR140, a novel zinc-finger protein with homology to the TAF250 subunit of TFIID. Biochem. Biophys. Res. Commun. 198: 1143-1152, 1994. [PubMed: 7906940] [Full Text: https://doi.org/10.1006/bbrc.1994.1162]