title: Overexpression of 14-3-3ζ Increases Brain Levels of C/EBP Homologous Protein CHOP.
abstract: Recent studies demonstrated that overexpression of the molecular chaperone 14-3-3ζ protects the brain against endoplasmic reticulum (ER) stress and prolonged seizures. The 14-3-3 targets responsible for improved neuronal survival after seizures remain unknown. Here we explored the mechanism, finding that protein levels of the ER-stress-associated transcription factor C/EBP homologous protein (CHOP) were significantly higher in 14-3-3ζ-overexpressing mice. Since previous studies by us demonstrated that loss of CHOP increased vulnerability to seizure damage, we explored whether elevated CHOP levels result from 14-3-3ζ overexpression and contribute to the protection. Pull-down experiments suggested that 14-3-3ζ could bind CHOP as well as sequester a CHOP-targeting microRNA. However, 14-3-3ζ overexpression remained protective against seizure-induced hippocampal injury in mice lacking CHOP. These studies reveal a novel function for 14-3-3ζ in regulating CHOP levels but show that this is not required for protection against seizure-induced neuronal death.
authors: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors: Gary P
authors: GP
authors: Brennan
authors: Eva M
authors: EM
authors: Jimenez-Mateos
authors: Amaya
authors: A
authors: Sanz-Rodriguez
authors: Claire M
authors: CM
authors: Mooney
authors: Guri
authors: G
authors: Tzivion
authors: David C
authors: DC
authors: Henshall
authors: Tobias
authors: T
authors: Engel
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D011485:Protein Binding; D013226:Status Epilepticus / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D035683:MicroRNAs; D051742:Transcription Factor CHOP; C000590975:Ywhaz protein, mouse; C497250:Ddit3 protein, mouse