AP-1 mediated retinal photoreceptor apoptosis is independent of N-terminal phosphorylation of c-Jun

Cell Death Differ. 2001 Aug;8(8):859-67. doi: 10.1038/sj.cdd.4400871.

Abstract

Apoptosis is essential for retinal development but it is also a major mode of cell loss in many human retinal dystrophies. High levels of visible light induce retinal apoptosis in mice and rats. This process is dependent on the induction of the transcription factor AP-1, a dimeric complex composed of c-Fos and c-Jun/JunD phosphoproteins. While c-Fos is essential, JunD is dispensable for light-induced photoreceptor apoptosis. Here we show that N-terminal phosphorylation of c-Jun, the other main partner of c-Fos in induced AP-1 complexes is not required for programmed cell death during retinal development in vivo and is also dispensable for photoreceptor apoptosis induced by the exogenous stimuli "excessive light" and N-nitroso-N-methylurea (MNU). Mice expressing a mutant c-Jun protein (JunAA) that cannot be phosphorylated at its N-terminus are apoptosis competent and their retina is not distinguishable from wild-type mice. Accordingly, Jun kinase, responsible for phosphorylation of wild-type c-Jun protein is at best only marginally induced by the apoptotic stimuli "light" and MNU. Complex composition of light-induced AP-1 complexes is similar in wild-type and JunAA mice. This shows that the mutant c-Jun protein can be part of the DNA binding complex AP-1 and demonstrates that induction of the DNA binding activity of AP-1 after light insult does not depend on N-terminal phosphorylation of c-Jun. Our results suggest that transactivation of target genes by phosphorylated c-jun/AP-1 is not required for MNU- or light-induced apoptosis of photoreceptor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Methylnitrosourea / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation / drug effects
  • Photic Stimulation
  • Photoreceptor Cells / cytology
  • Photoreceptor Cells / drug effects
  • Photoreceptor Cells / metabolism*
  • Protein Structure, Tertiary / drug effects
  • Protein Structure, Tertiary / genetics
  • Proto-Oncogene Proteins c-jun / drug effects
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Transcription Factor AP-1 / drug effects
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism*
  • Vision, Ocular / drug effects
  • Vision, Ocular / genetics

Substances

  • Alkylating Agents
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Methylnitrosourea
  • Mitogen-Activated Protein Kinase 8
  • Mitogen-Activated Protein Kinases