Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.
Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1) is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1) and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.
Animal Models of Aging, National Center for Geriatrics and Gerontology, Gengo, Obu, Aichi, Japan.
Young-Mi
YM
Lim
Shigeo
S
Hayashi
Leo
L
Tsuda
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D008297:Male; D009479:Neuropeptides / Q000235:genetics; D010786:Photoreceptor Cells / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D009479:Neuropeptides; D018808:Transcription Factor AP-1; C119014:ebi protein, Drosophila; D019204:GTP-Binding Proteins