title: JUN regulates early transcriptional responses to axonal injury in retinal ganglion cells.
abstract: The AP1 family transcription factor JUN is an important molecule in the neuronal response to injury. In retinal ganglion cells (RGCs), JUN is upregulated soon after axonal injury and disrupting JUN activity delays RGC death. JUN is known to participate in the control of many different injury response pathways in neurons, including pathways controlling cell death and axonal regeneration. The role of JUN in regulating genes involved in cell death, ER stress, and regeneration was tested to determine the overall importance of JUN in regulating RGC response to axonal injury. Genes from each of these pathways were transcriptionally controlled following axonal injury and Jun deficiency altered the expression of many of these genes. The differentially expressed genes included, Atf3, Ddit3, Ecel1, Gadd45α, Gal, Hrk, Pten, Socs3, and Sprr1a. Two of these genes, Hrk and Atf3, were tested for importance in RGC death using null alleles of each gene. Disruption of the prodeath Bcl2 family member Hrk did not affect the rate or amount of RGC death after axonal trauma. Deficiency in the ATF/CREB family transcription factor Atf3 did lessen the amount of RGC death after injury, though it did not provide long term protection to RGCs. Since JUN's dimerization partner determines its transcriptional targets, the expression of several candidate AP1 family members were examined. Multiple AP1 family members were induced by axonal injury and had a different expression profile in Jun deficient retinas compared to wildtype retinas (Fosl1, Fosl2 and Jund). Overall, JUN appears to play a multifaceted role in regulating RGC response to axonal injury.
authors: Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY, USA.
authors: Kimberly A
authors: KA
authors: Fernandes
authors: Jeffrey M
authors: JM
authors: Harder
authors: Jessica
authors: J
authors: Kim
authors: Richard T
authors: RT
authors: Libby
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000473:pathology*; D002452:Cell Count; D002470:Cell Survival; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D051700:Activating Transcription Factor 3; D051017:Apoptosis Regulatory Proteins; C103002:Atf3 protein, mouse; C107631:Hrk protein, mouse; D009479:Neuropeptides; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1
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