» Articles » PMID: 31891940

Hipk is Required for JAK/STAT Activity During Development and Tumorigenesis

Overview
Journal PLoS One
Date 2020 Jan 1
PMID 31891940
Citations 10
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Perilipin1 inhibits proliferation by promoting and mediated JAK-STAT pathway activation in .

Su Y, Qu Q, Li J, Han Z, Fang Y, Flavorta B Microbiol Spectr. 2024; 12(6):e0367123.

PMID: 38690912 PMC: 11237581. DOI: 10.1128/spectrum.03671-23.


The AMPK-like protein kinases Sik2 and Sik3 interact with Hipk and induce synergistic tumorigenesis in a cancer model.

Yu K, Ramkumar N, Wong K, Tettweiler G, Verheyen E Front Cell Dev Biol. 2023; 11:1214539.

PMID: 37854071 PMC: 10579798. DOI: 10.3389/fcell.2023.1214539.


Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.

Hogg E, Findlay G FEBS Lett. 2023; 597(19):2375-2415.

PMID: 37607329 PMC: 10952393. DOI: 10.1002/1873-3468.14723.


Transcriptome analysis of FOXO-dependent hypoxia gene expression identifies Hipk as a regulator of low oxygen tolerance in Drosophila.

Ding K, Barretto E, Johnston M, Lee B, Gallo M, Grewal S G3 (Bethesda). 2022; 12(12).

PMID: 36200850 PMC: 9713431. DOI: 10.1093/g3journal/jkac263.


Growth of T-cell lymphoma cells is inhibited by mPGES-1/PGE2 suppression via JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways.

Li Y, Qiu M, Li B, Xiao J, Yang W, Xie S Transl Cancer Res. 2022; 11(7):2175-2184.

PMID: 35966330 PMC: 9372224. DOI: 10.21037/tcr-21-2834.


References
1.
Lee W, Andrews B, Faust M, Walldorf U, Verheyen E . Hipk is an essential protein that promotes Notch signal transduction in the Drosophila eye by inhibition of the global co-repressor Groucho. Dev Biol. 2008; 325(1):263-72. DOI: 10.1016/j.ydbio.2008.10.029. View

2.
Jaszczak J, Halme A . Arrested development: coordinating regeneration with development and growth in Drosophila melanogaster. Curr Opin Genet Dev. 2016; 40:87-94. PMC: 5135572. DOI: 10.1016/j.gde.2016.06.008. View

3.
Wright V, Vogt K, Smythe E, Zeidler M . Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3. Cell Signal. 2011; 23(5):920-7. DOI: 10.1016/j.cellsig.2011.01.020. View

4.
Blaquiere J, Verheyen E . Homeodomain-Interacting Protein Kinases: Diverse and Complex Roles in Development and Disease. Curr Top Dev Biol. 2017; 123:73-103. DOI: 10.1016/bs.ctdb.2016.10.002. View

5.
Hanratty W, Dearolf C . The Drosophila Tumorous-lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus. Mol Gen Genet. 1993; 238(1-2):33-7. DOI: 10.1007/BF00279527. View