Haploinsufficiency or inactivating mutations of the human CUX1 gene have been associated with poor prognosis in a number of cancers, including myeloid malignancies. CUX1 belongs to a family of homeodomain-containing transcriptional regulators. There is a single ortholog of CUX1 in Drosophila, Dmel\ct, for which an extensive collection of classical loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\ct is also orthologous to a second human gene, CUX2.
The human Hsap\CUX1 has been introduced into flies, but has not been characterized in the context of this disease model. Heterologous rescue (functional complementation) of the ct wing phenotype is observed.
The identification of human CUX1 among several candidate genes within a haploinsufficient region associated with cancer progression was supported by data from Drosophila, using loss-of-function mutations of Dmel\ct. The hematopoietic system in Drosophila is composed of hemocytes with functions similar to human myeloid cells; haploinsufficiency of ct leads to hemocyte overproliferation and melanotic tumor formation. Many physical and genetic interactions of Dmel\ct have been described, see below and in the ct gene report.
[updated May 2018 by FlyBase; FBrf0222196]
The protein encoded by CUX1 is a member of the homeodomain family of DNA-binding proteins that appears to play a broad role in mammalian development as a transcriptional repressor of developmentally regulated gene expression. [Gene Cards, CUX1; 2018.05.08]
Work in Drosophila has led to the hypothesis that Cut transcription factors are involved in the coupling of differentiation and apoptosis, a cancer prevention mechanism resulting in the elimination of cells unable to differentiate (Zhai et al., 2012; FBrf0217859).
Many to one: 2 human to 1 Drosophila; the second human gene is CUX1.
Many to one: 2 human to 1 Drosophila; the second human gene is CUX2.
Moderate-scoring ortholog of human CUX1 and CUX2; Dmel\ct shares 22% identity and 32-36% similarity with the human genes.
