Up-regulation of Nucleolin mRNA and Protein in Peripheral Blood Mononuclear Cells by Extracellular-regulated Kinase*

The signal transduction pathways regulating nucleolin mRNA and protein production have yet to be elucidated. Peripheral blood mononuclear cells treated with phorbol 12-myristate 13-acetate showed steady state levels of nucleolin mRNA that were 2–2.5-fold greater than untreated control cells. The up-regulation of nucleolin mRNA was substantially repressed by U0126, a specific inhibitor that blocks phosphorylation of extracellular-regulated kinase (ERK). Calcium ionophores A23187 and ionomycin also activated ERK and substantially elevated nucleolin mRNA levels, demonstrating phorbol 12-myristate 13-acetate and calcium signaling converge on ERK. Drugs that affected protein kinase C, protein kinase A, and phospholipase C signal transduction pathways did not alter nucleolin mRNA levels significantly. The half-life of nucleolin mRNA increased from 1.8 h in resting cells to 3.2 h with phorbol ester activation, suggesting ERK-mediated posttranscriptional regulation. Concomitantly, full-length nucleolin protein was increased. The higher levels of nucleolin protein were accompanied by increased binding of a 70-kDa nucleolin fragment to the 29-base instability element in the 3′-untranslated region of amyloid precursor protein (APP) mRNA in gel mobility shift assays. Supplementation of rabbit reticulocyte lysate with nucleolin decreased APP mRNA stability and protein production. These data suggest ERK up-regulates nucleolin posttranscriptionally thereby controlling APP production.

[1]  J. Bonnet,et al.  IL-2-dependent expression of genes involved in cytoskeleton organization, oncogene regulation, and transcriptional control. , 1999, Journal of immunology.

[2]  A. Falaschi,et al.  Human DNA helicase VIII: a DNA and RNA helicase corresponding to the G3BP protein, an element of the ras transduction pathway. , 1999, Nucleic acids research.

[3]  E. López-Granados,et al.  Cellular Adhesion Mediated by Factor J, a Complement Inhibitor , 1998, The Journal of Biological Chemistry.

[4]  B. Dörken,et al.  Identification of Apoptosis-associated Proteins in a Human Burkitt Lymphoma Cell Line , 1998, The Journal of Biological Chemistry.

[5]  P. Sarnow,et al.  Viral Ribonucleoprotein Complex Formation and Nucleolar-Cytoplasmic Relocalization of Nucleolin in Poliovirus-Infected Cells , 1998, Journal of Virology.

[6]  P. Bouvet,et al.  Nucleolin Interacts with Several Ribosomal Proteins through Its RGG Domain* , 1998, The Journal of Biological Chemistry.

[7]  J. Malter,et al.  hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP mRNA. , 1998, Nucleic acids research.

[8]  P. Bouvet,et al.  Nucleolin functions in the first step of ribosomal RNA processing , 1998, The EMBO journal.

[9]  M. Yurkova,et al.  A Translation Regulatory Particle Containing theXenopus Oocyte Y Box Protein mRNP3+4* , 1997, The Journal of Biological Chemistry.

[10]  R. Wu,et al.  Isolation and characterization of nucleolin gene as one of the vitamin A-responsive genes in airway epithelium by a palindromic primer-based mRNA differential display method. , 1996, American journal of respiratory cell and molecular biology.

[11]  P. Bouvet,et al.  Nucleolin is a sequence-specific RNA-binding protein: characterization of targets on pre-ribosomal RNA. , 1996, Journal of molecular biology.

[12]  E. Krebs,et al.  The Physical Association of Casein Kinase 2 with Nucleolin* , 1996, The Journal of Biological Chemistry.

[13]  H. Kleinman,et al.  A 110‐kD nuclear shuttling protein, nucleolin, binds to the neurite‐promoting IKVAV site of laminin‐1 , 1995, Journal of neuroscience research.

[14]  D. Treré,et al.  The quantity of nucleolar proteins nucleolin and protein B23 is related to cell doubling time in human cancer cells. , 1995, Laboratory investigation; a journal of technical methods and pathology.

[15]  J. Malter,et al.  Nucleolin and Heterogeneous Nuclear Ribonucleoprotein C Proteins Specifically Interact with the 3′-Untranslated Region of Amyloid Protein Precursor mRNA (*) , 1995, The Journal of Biological Chemistry.

[16]  K. Higashi,et al.  Induction of heat shock protein 70 and nucleolin and their intracellular distribution during early stage of liver regeneration. , 1995, Journal of biochemistry.

[17]  G. Méhes,et al.  Nucleolin and fibrillarin expression in stimulated lymphocytes and differentiating HL‐60 cells. A flow cytometric assay , 1995, Cell proliferation.

[18]  S. Yamawaki,et al.  Imipramine stimulates phospholipase C activity in rat brain , 1994, Neurochemistry International.

[19]  T. Arima,et al.  Identification of nucleolin as a binding protein for midkine (MK) and heparin-binding growth associated molecule (HB-GAM). , 1994, Journal of biochemistry.

[20]  J. Malter,et al.  Multiple proteins interact at a unique cis-element in the 3'-untranslated region of amyloid precursor protein mRNA. , 1994, The Journal of biological chemistry.

[21]  M. Lai,et al.  Purification and characterization of nucleolin and its identification as a transcription repressor , 1994, Molecular and cellular biology.

[22]  S. Fang,et al.  The self-cleaving activity of nucleolin determines its molecular dynamics in relation to cell proliferation. , 1993, Experimental cell research.

[23]  G. Dreyfuss,et al.  Nuclear proteins that bind the pre-mRNA 3' splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n , 1993, Molecular and cellular biology.

[24]  C. Kahn,et al.  Insulin induces the phosphorylation of nucleolin. A possible mechanism of insulin-induced RNA efflux from nuclei. , 1993, The Journal of biological chemistry.

[25]  F. Amalric,et al.  Concerted activities of the RNA recognition and the glycine-rich C-terminal domains of nucleolin are required for efficient complex formation with pre-ribosomal RNA. , 1992, European journal of biochemistry.

[26]  F. Amalric,et al.  The glycine-rich domain of nucleolin has an unusual supersecondary structure responsible for its RNA-helix-destabilizing properties. , 1992, The Journal of biological chemistry.

[27]  R. Petryshyn,et al.  Phosphorylation and proteolytic degradation of nucleolin from 3T3-F442A cells. , 1991, Biochemical and biophysical research communications.

[28]  M. Pasternack,et al.  Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro. , 1991, The Journal of biological chemistry.

[29]  K. Higashi,et al.  Down modulation of N-myc, heat-shock protein 70, and nucleolin during the differentiation of human neuroblastoma cells. , 1991, Journal of biochemistry.

[30]  C. Chen,et al.  Increased stability of nucleolin in proliferating cells by inhibition of its self-cleaving activity. , 1991, The Journal of biological chemistry.

[31]  C. Semenkovich,et al.  A protein partially expressed on the surface of HepG2 cells that binds lipoproteins specifically is nucleolin. , 1990, Biochemistry.

[32]  O. Mcbride,et al.  Genomic organization and chromosomal localization of the human nucleolin gene. , 1990, The Journal of biological chemistry.

[33]  T. Nakamura,et al.  Simultaneous activation of heat shock protein (hsp 70) and nucleolin genes during in vivo and in vitro prereplicative stages of rat hepatocytes. , 1990, Experimental cell research.

[34]  J. Labbé,et al.  Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase , 1990, Molecular and cellular biology.

[35]  M. Kirstein,et al.  Limited proteolysis as a probe of the conformation and nucleic acid binding regions of nucleolin. , 1990, Biochemistry.

[36]  V. Baldin,et al.  Glucocorticoids repress ribosome biosynthesis in lymphosarcoma cells by affecting gene expression at the level of transcription, posttranscription and translation. , 1990, Biochimica et biophysica acta.

[37]  J. Labbé,et al.  Identification of major nucleolar proteins as candidate mitotic substrates of cdc2 kinase , 1990, Cell.

[38]  J. Malter,et al.  Identification of an AUUUA-specific messenger RNA binding protein. , 1989, Science.

[39]  O. Issinger,et al.  Growth-dependent modulation of casein kinase II and its substrate nucleolin in primary human cell cultures and HeLa cells. , 1989, Biochimica et biophysica acta.

[40]  H. Prats,et al.  Protein kinase NII and the regulation of rDNA transcription in mammalian cells. , 1989, Nucleic acids research.

[41]  H. Pollard,et al.  Cloning and sequencing of the human nucleolin cDNA , 1989, FEBS letters.

[42]  C. Lehner,et al.  Major nucleolar proteins shuttle between nucleus and cytoplasm , 1989, Cell.

[43]  E. Egyházi,et al.  Effects of anti-C23 (nucleolin) antibody on transcription of ribosomal DNA in Chironomus salivary gland cells. , 1988, Experimental cell research.

[44]  F. Amalric,et al.  A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1. , 1988, European journal of biochemistry.

[45]  F. Amalric,et al.  Phosphorylation of nucleolin by a nucleolar type NII protein kinase. , 1987, Biochemistry.

[46]  Gwyn Jordan.  At the heart of the nucleolus , 1987, Nature.

[47]  H. Bourbon,et al.  RNA binding fragments from nucleolin contain the ribonucleoprotein consensus sequence. , 1987, The Journal of biological chemistry.

[48]  H. Bourbon,et al.  Nucleolin, the major nucleolar protein of growing eukaryotic cells: an unusual protein structure revealed by the nucleotide sequence. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[49]  S. H. Ghaffari,et al.  Protein and cDNA sequence of a glycine-rich, dimethylarginine-containing region located near the carboxyl-terminal end of nucleolin (C23 and 100 kDa). , 1986, The Journal of biological chemistry.

[50]  R. Richards,et al.  Localization of phosphoprotein C23 to nucleolar structures and to the nucleolus organizer regions. , 1981, Experimental cell research.

[51]  G. Serin,et al.  Localization of nucleolin binding sites on human and mouse pre-ribosomal RNA. , 1996, Biochimie.

[52]  S. Pongor,et al.  Human DNA helicase IV is nucleolin, an RNA helicase modulated by phosphorylation. , 1995, Gene.