Experiments in Drosophila in a number of different tissue types support a role of the fly Hipk gene in hyperplasia and tumorigenesis. There are three HIPK (homeodomain interacting protein kinase) genes in human, HIPK1, HIPK2, and HIPK3; HIPK1 has been associated with breast cancer in a GWAS study. The HIPK proteins are serine/threonine-protein kinases involved in many regulatory functions, as transcriptional co-regulators and as modifiers of regulatory proteins. There is a single HIPK gene in Drosophila, Dmel\Hipk, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and loss-of-function mutations caused by imprecise excision of TE insertions have been generated.
None of the human HIPK genes has been introduced into flies.
Elevated expression of Dmel\Hipk induces hyperplasia in imaginal discs and hemocytes, leading to massive tissue growth and melanotic tumor-like masses, respectively. In imaginal discs, evidence of degradation of the basement membrane and induction of epithelial-to-mesenchymal transition is observed. Several observations suggest invasive cell behavior: when Hipk is overexpressed in the adult eye, ectopic eye tissue is observed in the thorax or abdomen; in imaginal discs, small numbers of Hipk-expressing cells are observed to cross the A/P compartment boundary. Regions with high amounts of ectopic Hipk show elevated levels of Myc as well, which is a potent oncogene associated with many cancer models (FBhh0000402). Tumor cells expressing both Hipk and Myc have high levels of aerobic glycolysis (the Warburg effect), a feature of many aggressive cancers (FBhh0000959).
Animals homozygous for loss-of-function mutations of Dmel\Hipk die during the larval or pupal stages. Physical and genetic interactions have been described for Dmel\Hipk; see below and in the Hipk gene report.
[updated September 2019 by FlyBase; FBrf0222196]
HIPK1 is associated with breast cancer in a GWAS study (see GWAS Catalog, below in 'External links').
The HIPK proteins are serine/threonine-protein kinases involved in transcriptional regulation and regulation of apoptosis. They interact with homeodomain transcription factors, other transcription factors, and other regulatory proteins. Promote apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level. [Gene Cards, HIPK1, HIPK2, HIPK3; 2018.02.23]
Many to one: 3 human to 1 Drosophila; the human genes are HIPK1, HIPK2, and HIPK3.
Many to one: 3 human to 1 Drosophila; the human genes are HIPK1, HIPK2, and HIPK3.
Many to one: 3 human to 1 Drosophila; the human genes are HIPK1, HIPK2, and HIPK3.
Moderate-scoring ortholog of human HIPK1, HIPK2, and HIPK3 (1 Drosophila to 3 human). Dmel\Hipk shares 35-37% identity and 46-47% similarity with the human genes.
