Hepatoma-derived Growth Factor Stimulates Cell Growth after Translocation to the Nucleus by Nuclear Localization Signals
Autor: | Yoshitaka Izumoto, Yoshihiko Kishima, Hiroyasu Yamamoto, Toshifumi Kuroda, Kazuyuki Yoshizaki, Mitsunari Yamamoto, Kenya Yoshida, Hiroaki Ito, Hideji Nakamura, Hirayuki Enomoto |
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Rok vydání: | 2002 |
Předmět: |
Cytoplasm
Time Factors Recombinant Fusion Proteins Amino Acid Motifs Blotting Western Green Fluorescent Proteins Molecular Sequence Data Nuclear Localization Signals Active Transport Cell Nucleus Biology Polymerase Chain Reaction Biochemistry Cell Line Green fluorescent protein Mice medicine Animals Humans NLS Amino Acid Sequence Growth Substances Molecular Biology Peptide sequence Alleles Cell Nucleus 3T3 Cells DNA Cell Biology Hepatoma-derived growth factor Molecular biology Protein Structure Tertiary Luminescent Proteins Protein Transport Cell nucleus medicine.anatomical_structure Microscopy Fluorescence Mutation Mutagenesis Site-Directed Intercellular Signaling Peptides and Proteins Tumor Suppressor Protein p53 Nucleus Cell Division Gene Deletion Nuclear localization sequence Plasmids |
Zdroj: | Journal of Biological Chemistry. 277:10315-10322 |
ISSN: | 0021-9258 |
Popis: | Hepatoma-derived growth factor (HDGF) is the original member of the HDGF family of proteins, which contains a well-conserved N-terminal amino acid sequence (homologous to the amino terminus of HDGF; hath) and nuclear localization signals (NLSs) in gene-specific regions other than the hath region. In addition to a bipartite NLS in a gene-specific region, an NLS-like sequence is also found in the hath region. In cells expressing green fluorescence protein (GFP)-HDGF, green fluorescence was observed in the nucleus, whereas it was detected in the cytoplasm of cells expressing GFP-HDGF with both NLSs mutated or deleted. GFP-hath protein (GFP-HATH) was distributed mainly in the nucleus, although some was present in the cytoplasm, whereas GFP-HDGF with a deleted hath region (HDGFnonHATH) was found only in the nucleus. Exogenously supplied GFP-HDGF was internalized and translocated to the nucleus. GFP-HATH was internalized, whereas GFP-HDGFnonHATH was not. Overexpression of HDGF stimulated DNA synthesis and cellular proliferation, although HDGF with both NLSs deleted did not. Overexpression of HDGFnonHATH caused a significant stimulation of DNA synthesis, whereas that of hath protein did not. HDGF containing the NLS sequence of p53 instead of the bipartite NLS did not stimulate DNA synthesis, and truncated forms without the C- or N-terminal side of NLS2 did not. These findings suggest that the gene-specific region, at least the bipartite NLS sequence and the N- and C-terminal neighboring portions, is essential for the mitogenic activity of HDGF after nuclear translocation. |
Databáze: | OpenAIRE |
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