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Crosstalk between NRF2 and HIPK2 shapes cytoprotective responses
L Torrente1, C Sanchez1, R Moreno1
1Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
Oncogene
|July 11, 2017
Summary
Homeodomain interacting protein kinase-2 (HIPK2) is regulated by the transcription factor NRF2. This study reveals HIPK2
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- Homeodomain interacting protein kinase-2 (HIPK2) is a stress-responsive kinase with known tumor suppressor roles.
- Recent findings suggest HIPK2 may also promote tumor progression through unknown mechanisms.
- The transcription factor NRF2 is a key regulator of cytoprotective responses.
Purpose of the Study:
- To investigate the relationship between HIPK2 and NRF2.
- To elucidate the regulatory mechanisms and functional consequences of HIPK2-NRF2 crosstalk.
- To explore the therapeutic potential of targeting this pathway in cancer.
Main Methods:
- Identification of NRF2 binding site in the HIPK2 gene locus.
- Transcriptional analysis of HIPK2 regulation by NRF2.
- Gain-of-function and loss-of-function experiments to assess HIPK2's role in NRF2-mediated cytoprotection.
- In vitro and in vivo studies.
Main Results:
- HIPK2 is a direct transcriptional target of NRF2, establishing a novel regulatory axis.
- HIPK2 is essential for effective NRF2-mediated cellular and in vivo responses.
- HIPK2 elicits cytoprotective effects in cancer cells through NRF2.
- NRF2 activation in tumors correlates with chemoresistance and poor prognosis.
Conclusions:
- Discovered a novel downstream effector of HIPK2: the transcription factor NRF2.
- HIPK2 modulates NRF2 activity, influencing cancer cell survival and chemoresistance.
- Targeting HIPK2 or NRF2 signaling presents a potential strategy to enhance chemotherapy efficacy.
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