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The Journal of Neuroscience, December 15, 1999, 19(24):10747-10756
Protein 4.1N Binding to Nuclear Mitotic Apparatus Protein in PC12 Cells Mediates the Antiproliferative Actions of Nerve Growth Factor
Keqiang Ye1, Duane A. Compton2, Michael M. Lai1, Loren D. Walensky1, and Solomon H. Snyder1 1 Departments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and 2 Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755
Protein 4.1N is a neuronal selective isoform of the erythrocyte membrane cytoskeleton protein 4.1R. In the present study, we demonstrate an interaction between 4.1N and nuclear mitotic apparatus protein (NuMA), a nuclear protein required for mitosis. The binding involves the C-terminal domain of 4.1N. In PC12 cells treatment with nerve growth factor (NGF) elicits translocation of 4.1N to the nucleus and promotes its association with NuMA. Specific targeting of 4.1N to the nucleus arrests PC12 cells at the G1 phase and produces an aberrant nuclear morphology. Inhibition of 4.1N nuclear translocation prevents the NGF-mediated arrest of cell division, which can be reversed by overexpression of 4.1N. Thus, nuclear 4.1N appears to mediate the antiproliferative actions of NGF by antagonizing the role of NuMA in mitosis.
Key words: 4.1N; nuclear mitotic apparatus protein (NuMA); nerve growth factor (NGF); nuclear translocation; G1 phase arrest; mitosis
Copyright © 1999 Society for Neuroscience 0270-6474/99/192410747-10$05.00/0
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