Human Molecular Genetics, 2002, Vol. 11, No. 22 2723-2733
© 2002 Oxford University Press
The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1
1Center for Genome Information, Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA, 2The Mary D. Allen Laboratory for Vision Research, Doheny Eye Institute, Department of Cell and Neurobiology, the Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA, 3Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA, 4Department of Ophthalmology and 5Department of Pathology, Columbia University, 630 West 168th Street, New York, NY 10032, USA, 6Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA, 7Division of Molecular Medicine, 8Human Genetics Center, School of Public Health, and Department of Ophthalmology and Visual Science and 9Department of Cardiology, M. D. Anderson Cancer Center, The University of Texas–Houston Health Science Center, Houston, TX 77030, USA
Received June 4, 2002; Accepted August 16, 2002
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.
* To whom correspondence should be addressed at: Department of Ophthalmology, Columbia University, 630 West 168th Street, New York, NY 10032, USA. Tel: +1 2123054854; Fax: +1 2123421883; Email: ms2241{at}columbia.edu
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