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.
Chittka
A
A
Cell Biology Program, Weill Graduate School of Cornell University Medical College, New York, NY 10021, USA.
Chao
M V
MV
D000595:Amino Acid Sequence; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism*; D020933:Neurotrophin 3; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014157:Transcription Factors; D016335:Zinc Fingers
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D009687:Nuclear Proteins; C121661:Prdm4 protein, rat; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D001973:Bromodeoxyuridine