Protein 4.1N binding to nuclear mitotic apparatus protein in PC12 cells mediates the antiproliferative actions of nerve growth factor

Keqiang Ye, Duane A. Compton, Michael M. Lai, Loren D. Walensky, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10747-10756
Number of pages10
JournalJournal of Neuroscience
Volume19
Issue number24
DOIs
StatePublished - Dec 15 1999

Keywords

  • 4.1N
  • G1 phase arrest
  • Mitosis
  • Nerve growth factor (NGF)
  • Nuclear mitotic apparatus protein (NUMA)
  • Nuclear translocation

ASJC Scopus subject areas

  • Neuroscience(all)

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