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Crosstalk between NRF2 and HIPK2 shapes cytoprotective responses.
Torrente, L; Sanchez, C; Moreno, R; Chowdhry, S; Cabello, P; Isono, K; Koseki, H; Honda, T; Hayes, J D; Dinkova-Kostova, A T; de la Vega, L.
Afiliação
  • Torrente L; Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
  • Sanchez C; Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
  • Moreno R; Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
  • Chowdhry S; Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
  • Cabello P; Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
  • Isono K; Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
  • Koseki H; Developmental Genetics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
  • Honda T; Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, USA.
  • Hayes JD; Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
  • Dinkova-Kostova AT; Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
  • de la Vega L; Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, James Arrott Drive, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
Oncogene ; 36(44): 6204-6212, 2017 11 02.
Article em En | MEDLINE | ID: mdl-28692050
Homeodomain interacting protein kinase-2 (HIPK2) is a member of the HIPK family of stress-responsive kinases that modulates cell growth, apoptosis, proliferation and development. HIPK2 has several well-characterised tumour suppressor roles, but recent studies suggest it can also contribute to tumour progression, although the underlying mechanisms are unknown. Herein, we have identified novel crosstalk between HIPK2 and the cytoprotective transcription factor NRF2. We show that HIPK2 is a direct transcriptional target of NRF2, identifying a functional NRF2 binding site in the HIPK2 gene locus and demonstrating for the first time a transcriptional mode of regulation for this kinase. In addition, HIPK2 is required for robust NRF2 responsiveness in cells and in vivo. By using both gain-of-function and loss-of-function approaches, we demonstrate that HIPK2 can elicit a cytoprotective response in cancer cells via NRF2. Our results have uncovered a new downstream effector of HIPK2, NRF2, which is frequently activated in human tumours correlating with chemoresistance and poor prognosis. Furthermore, our results suggest that modulation of either HIPK2 levels or activity could be exploited to impair NRF2-mediated signalling in cancer cells, and thus sensitise them to chemotherapeutic drugs.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Transporte / Proteínas Serina-Treonina Quinases / Proliferação de Células / Fator 2 Relacionado a NF-E2 / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Oncogene Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Transporte / Proteínas Serina-Treonina Quinases / Proliferação de Células / Fator 2 Relacionado a NF-E2 / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Oncogene Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido