Identification of a zinc finger protein whose subcellular distribution is regulated by serum and nerve growth factor

Identification of a zinc finger protein whose subcellular distribution is regulated by serum and nerve growth factor

Alexandra Chittka*,† and
Moses V. Chao*,‡

^*Cell Biology Program, Weill Graduate School of Cornell University Medical College, New York, NY 10021, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016

Edited by Michael V. L. Bennett, Albert Einstein College of Medicine, Woods Hole, MA, and approved July 13, 1999 (received for review March 24, 1999)

Abstract

A subclass of zinc finger proteins containing a unique protein motif called the positive regulatory (PR) domain has been described. The members include the PRDI-BF1/Blimp-1 protein, the Caenorhabditis elegans egl-43 and EVI1 gene products, and the retinoblastoma interacting protein RIZ. Here we describe a member of this family, SC-1, that exhibits several distinctive features. First, SC-1 interacts with the p75 neurotrophin receptor and is redistributed from the cytoplasm to the nucleus after nerve growth factor (NGF) treatment of transfected COS cells. The translocation of SC-1 to the nucleus was specific for p75, as NGF binding to the TrkA receptor did not lead to nuclear localization of SC-1. Thus, SC-1 provides a downstream transducer for the effects of NGF through the p75 neurotrophin receptor. Under normal growth conditions, SC-1 was found predominantly in the cytoplasm. On serum-starvation, SC-1 also translocated into the nucleus. A direct correlation between nuclear expression of SC-1 with the loss of BrdUrd incorporation was observed. These results imply that SC-1 may be involved in events associated with growth arrest.

Footnotes

↵ † Present address: Biozentrum, University of Wurzburg, 97074 Wurzburg, Germany.
↵ ‡ To whom reprint requests should be addressed at: Molecular Neurobiology Program, Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016. E-mail: chao{at}saturn.med.nyu.edu.
This paper was submitted directly (Track II) to the Proceedings Office.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF176023).
ABBREVIATIONS:

NGF,

nerve growth factor;

PR domain,

positive regulatory domain;

kb,

kilobase;

GST,

glutathione S-transferase