title: The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1.
abstract: Mutations in the aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) gene have been found in patients with Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. To determine the normal function of AIPL1 and to better understand how mutations in this gene cause disease, we performed a yeast two-hybrid screen to identify AIPL1-interacting proteins in the retina. One of the identified interacting proteins corresponds to NUB1 (NEDD8 Ultimate Buster 1), which is thought to control many biological events, especially cell cycle progression, by downregulating NEDD8 expression. The AIPL1-NUB1 interaction was verified by co-immunoprecipitation studies in Y79 retinoblastoma cells, demonstrating that this interaction occurs within cells that share a number of features with retinal progenitor cells. Furthermore, we examined the localization of the AIPL1 protein within developing and adult retinas, and found that AIPL1 is present in the developing photoreceptor layer of the human retina and within the photoreceptors of the adult retina. Similar to AIPL1, NUB1 is also expressed in the developing and adult retina. Therefore, it is possible that the early-onset form of retinal degeneration seen in LCA patients with AIPL1 mutations may be due to a defect in the regulation of cell cycle progression during photoreceptor maturation. These data raise the possibility that AIPL1 is important for appropriate photoreceptor formation during development and/or survival following differentiation.
authors.affiliation: Center for Genome Information, Department of Environmental Health, University of Cincinnati, OH 45267, USA.
authors.forename: Dayna T
authors.initials: DT
authors.lastname: Akey
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhu
authors.forename: Michael
authors.initials: M
authors.lastname: Dyer
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.forename: Adam
authors.initials: A
authors.lastname: Sorensen
authors.forename: Seth
authors.initials: S
authors.lastname: Blackshaw
authors.forename: Taeko
authors.initials: T
authors.lastname: Fukuda-Kamitani
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Daiger
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Craft
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kamitani
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Sohocki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: C403625:AIPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C498604:Aipl1 protein, mouse; D002352:Carrier Proteins; D005136:Eye Proteins; C430242:NUB1 protein, human; C486597:Nub1 protein, mouse; D011994:Recombinant Proteins; D014157:Transcription Factors