Protein 4.1N binding to nuclear mitotic apparatus protein in PC12 cells mediates the antiproliferative actions of nerve growth factor.
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.
Ye
K
K
Departments of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Compton
D A
DA
Lai
M M
MM
Walensky
L D
LD
Snyder
S H
SH
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology; D008565:Membrane Proteins; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009479:Neuropeptides / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells / Q000378:metabolism* / Q000473:pathology; D051381:Rats
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; C489081:Numa1 protein, rat; C120557:erythrocyte membrane protein band 4.1-like 1; D020932:Nerve Growth Factor