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

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.