A pathway from JNK through decreased ERK and Akt activities for FOXO3a nuclear translocation in response to UV irradiation

J Cell Physiol. 2012 Mar;227(3):1168-78. doi: 10.1002/jcp.22839.

Abstract

Forkhead box O (FOXO) transcription factors play an important role in physiological and pathological processes. Extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) can phosphorylate FOXO and cause its degradation or cytoplasmic retention, respectively, leading to tumorigenesis. In addition, C-Jun N-terminal protein kinase (JNK) can promote FOXO nuclear localization, leading to apoptosis. Using confocal imaging of cells transfected with GFP-FOXO3a, we visualized the dynamic translocation of GFP-FOXO3a from the cytoplasm to the nucleus after UV irradiation in a time- and dose-dependent manner. We also found that UV irradiation caused activation of JNK, which in turn inactivated ERK and Akt, leading to FOXO3a translocation and Bim expression. Our results indicate that nuclear translocation of FOXO3a can be regulated by UV irradiation through the JNK-ERK/Akt pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Adenocarcinoma of Lung
  • Apoptosis / physiology
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Down-Regulation / physiology
  • Down-Regulation / radiation effects
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / physiology*
  • Extracellular Signal-Regulated MAP Kinases / radiation effects
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / physiology*
  • Forkhead Transcription Factors / radiation effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / physiology*
  • Lung Neoplasms
  • MAP Kinase Signaling System / physiology
  • MAP Kinase Signaling System / radiation effects*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / physiology*
  • Proto-Oncogene Proteins c-akt / radiation effects
  • RNA Interference
  • Ultraviolet Rays / adverse effects*

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases