Hipk Is Required For JAK/STAT Activity during Development and Tumorigenesis

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Tettweiler G, Blaquiere JA, Wray NB, Verheyen EM (2019) Hipk is required for JAK/STAT activity during development and tumorigenesis. PLoS ONE 14(12): e0226856. DOI: 10.1371/journal.pone.0226856.

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Drosophila has been instrumental as a model system in studying signal transduction and revealing molecular functions in development and human diseases. A point mutation in the Drosophila Janus kinase JAK (called hop) causes constitutive activation of the JAK/STAT pathway. We provide robust genetic evidence that the Homeodomain interacting protein kinase (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. Further, the loss of the pathway effector Stat92E can suppress Hipk induced overgrowth. Interaction studies show that Hipk can physically interact with Stat92E and regulate Stat92E subcellular localization. Together our results show that Hipk is a novel factor required for effective JAK/STAT signaling.

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