# The homeodomain-interacting protein kinase Hipk promotes apoptosis by stabilizing the active form of Dronc

**Authors:** Juan Manuel García-Arias, Rafael Alejandro Juárez-Uribe, Luis Alberto Baena-López, Ginés Morata, Ernesto Sánchez-Herrero

PMC · DOI: 10.1038/s41420-025-02916-9 · Cell Death Discovery · 2025-12-16

## TL;DR

The Hipk protein helps control cell death by keeping the Dronc protein active, which is important for triggering apoptosis and strengthening related signaling pathways.

## Contribution

Hipk stabilizes Dronc's active form, enhancing caspase cascade induction and JNK signaling in apoptosis.

## Key findings

- Hipk is necessary for stabilizing the initiator caspase Dronc in apoptotic scenarios.
- Dronc raises Hipk expression levels, reinforcing the apoptotic response.
- Hipk's role in caspase regulation could make it a target for modulating apoptosis in various contexts.

## Abstract

Members of the evolutionarily conserved homeodomain-interacting protein kinase (Hipk) family play a critical role in regulating essential signalling pathways involved in growth, differentiation, and apoptosis. While vertebrates have multiple hipk genes, Drosophila contains a single hipk ortholog, what facilitates functional analysis. We find that hipk is necessary for the stabilization of the initiator caspase Dronc, thus enhancing the two Dronc activities in apoptotic scenarios: the induction of the caspase cascade, and the reinforcement of JNK signalling pathway. Conversely, our data suggest that Dronc also raises the expression levels of Hipk, thereby reinforcing the apoptotic response. These findings significantly enhance our understanding of caspase regulation and position Hipk as a promising target for modulating caspase activity in a variety of biological contexts.

## Linked entities

- **Genes:** Hipk (Homeodomain interacting protein kinase) [NCBI Gene 38070], Dronc (Death regulator Nedd2-like caspase) [NCBI Gene 39173]
- **Proteins:** Hipk (Homeodomain interacting protein kinase), Dronc (Death regulator Nedd2-like caspase)
- **Species:** Drosophila (taxon 7215)

## Full-text entities

- **Genes:** Hipk (Homeodomain interacting protein kinase) [NCBI Gene 38070] {aka CG17090, DHIPK2, Dmel\CG17090, HIPK2, dhipk2}, Dronc (Death regulator Nedd2-like caspase) [NCBI Gene 39173] {aka CG8090, CG8091, Dmel\CG8091, Dronc/Casp9, Nc, Nc\Dronc}, Dcp-1 (Death caspase-1) [NCBI Gene 37729] {aka CG5370, DCP1, Dcp1, Dmel\CG5370, cDcp, cDcp-1}, bsk (basket) [NCBI Gene 44801] {aka Basket, CG5680, D-JNK, D-junk, DBSK/JNK, DJNK}
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12848060/full.md

## References

3 references — full list in the complete paper: https://tomesphere.com/paper/PMC12848060/full.md

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Source: https://tomesphere.com/paper/PMC12848060