Transition of localization of the N-Myc protein from nucleus to cytoplasm in differentiating neurons

N-myc is a developmentally regulated proto-oncogene encoding a putative sequence-specific DNA-binding protein. Previous studies on tissue distribution of N-myc transcripts indicated that one of the major sites of N-myc expression is the CNS and neural crest derivatives in developing embryos. We investigated N-Myc protein expression in embryonic neural tissues and found that the protein was usually localized in the nucleus, but accumulated in the cytoplasm upon differentiation of specific classes of neurons, e.g., retinal ganglion cells, neurons of spinal ganglia, and Purkinje cells of the cerebellum. The change of localization of N-Myc from the nucleus to the cytoplasm indicates a novel feature of regulation of myc family proteins and suggests functions of N-myc in the cytoplasm of maturing neurons.

[1]  H. Kondoh,et al.  Tissue Distribution of N‐myc Expression in the Early Organogenesis Period of the Mouse Embryo , 1991, Development, growth & differentiation.

[2]  K. Kato,et al.  Rapid and transient decrease of N-myc expression in retinoic acid-induced differentiation of OTF9 teratocarcinoma stem cells. , 1990, Molecular and cellular biology.

[3]  R. Steward Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function , 1989, Cell.

[4]  R. A. Murphy,et al.  Detection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: Inhibition by antibodies to NGF , 1991, Neuron.

[5]  R. Akeson,et al.  N-myc down regulates neural cell adhesion molecule expression in rat neuroblastoma , 1990, Molecular and cellular biology.

[6]  K. Kato,et al.  Organization and expression of the chicken N-myc gene , 1990, Molecular and cellular biology.

[7]  G. D. Johnson,et al.  A simple method of reducing the fading of immunofluorescence during microscopy. , 1981, Journal of immunological methods.

[8]  C. Nüsslein-Volhard,et al.  A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo , 1989, Cell.

[9]  D. Baltimore,et al.  Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-κB transcription factor , 1988, Cell.

[10]  R. Weinberg,et al.  N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma , 1986, Cell.

[11]  T. Boone,et al.  Identification and characterization of the protein encoded by the human N-myc oncogene. , 1986, Science.

[12]  E. R. Sánchez Heat shock induces translocation to the nucleus of the unliganded glucocorticoid receptor. , 1992, The Journal of biological chemistry.

[13]  L. Neckers,et al.  Episome-generated N-myc antisense RNA restricts the differentiation potential of primitive neuroectodermal cell lines , 1991, Molecular and cellular biology.

[14]  F. Alt,et al.  Structure and expression of canary myc family genes , 1991, Molecular and cellular biology.

[15]  M. Sieber-Blum Role of the neurotrophic factors BDNF and NGF in the commitment of pluripotent neural crest cells , 1991, Neuron.

[16]  T. Soussi,et al.  Translocation of a store of maternal cytoplasmic c-myc protein into nuclei during early development , 1989, Molecular and cellular biology.

[17]  A. Capobianco,et al.  Cloning and expression of a chicken c-rel cDNA: unlike p59v-rel, p68c-rel is a cytoplasmic protein in chicken embryo fibroblasts. , 1990, Oncogene.

[18]  K. Alitalo,et al.  Alternative Forms of Max as Enhancers or Suppressors of Myc-Ras Cotransformation , 1992, Science.

[19]  P. Roux,et al.  Nuclear localization of c-Fos, but not v-Fos proteins, is controlled by extracellular signals , 1990, Cell.

[20]  D. Baltimore,et al.  Activation in vitro of NF-κB" by phosphorylation of its inhibitor IκB" , 1990, Nature.

[21]  Y. Miyata,et al.  Cytoplasmic 8 S glucocorticoid receptor binds to actin filaments through the 90-kDa heat shock protein moiety. , 1991, The Journal of biological chemistry.

[22]  U. Zabel,et al.  Purified human IκB can rapidly dissociate the complex of the NF-κB transcription factor with its cognate DNA , 1990, Cell.

[23]  F. Alt,et al.  Differential expression of myc family genes during murine development , 1986, Nature.

[24]  J. Bishop,et al.  Contrasting patterns of myc and N-myc expression during gastrulation of the mouse embryo. , 1989, Genes & development.

[25]  D. Baltimore,et al.  I kappa B: a specific inhibitor of the NF-kappa B transcription factor. , 1988, Science.

[26]  B. Vandenbunder,et al.  In situ study of c-myc protein expression during avian development. , 1989, Development.

[27]  H. Kondoh,et al.  Subnuclear localization and antitransforming activity of N-myc:beta-galactosidase fusion proteins , 1988, Molecular and cellular biology.

[28]  J. Trent,et al.  Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour , 1983, Nature.

[29]  N. Nakatsuji,et al.  A mouse embryonic stem cell line showing pluripotency of differentiation in early embryos and ubiquitous beta-galactosidase expression. , 1990, Cell differentiation and development : the official journal of the International Society of Developmental Biologists.

[30]  G. Prendergast,et al.  Association of Myn, the murine homolog of Max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation , 1991, Cell.

[31]  F. Alt,et al.  N-myc proto-oncogene expression during organogenesis in the developing mouse as revealed by in situ hybridization , 1988, The Journal of cell biology.

[32]  M. Schwab,et al.  Expression of N-myc in teratocarcinoma stem cells and mouse embryos , 1985, Nature.

[33]  M. Levine,et al.  The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila , 1989, Cell.

[34]  F. Alt,et al.  Transposition and amplification of oncogene-related sequences in human neuroblastomas , 1983, Cell.