Hipk is required for JAK/STAT activity and promotes hemocyte-derived tumorigenesis

Dysregulation of key signaling molecules and pathways are causative of many Human diseases and cancers. A point mutation in the Drosophila Janus kinase (called hop ) causes constitutive activation of the JAK/STAT pathway and results in blood cell tumours. We provide robust genetic evidence that Hipk is required for endogenous JAK/STAT activity. Overexpression of Hipk can phenocopy the effects of overactive JAK/STAT mutations and lead to melanized tumors and loss of Hipk can suppress the effects of hyperactive JAK/STAT. Furthermore, Hipk expression in blood cell progenitors causes tumors. PLA experiments show that Hipk can interact with the pathway effector Stat92E. Together our results show that Hipk is a novel factor required for effective JAK/STAT signaling. Summary Statement Loss of hipk impairs JAK/STAT activity in multiple tissue types and elevated Hipk leads to the formation of blood cell tumors in Drosophila.