Linked Life Data

14970216

Source:http://linkedlifedata.com/resource/pubmed/id/14970216

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2004-4-19
pubmed:abstractText
It is widely held that growth factor signaling is terminated by lysosomal degradation of its activated receptor and the endocytosed growth factor is transported to lysosomes. Nuclear targeting is another important pathway through which signals of growth factors are mediated. However, mechanisms underlying desensitization of nuclear targeting growth factors are poorly understood. Here we report that the nuclear targeting pathway is down-regulated by the proteasome system. Degradation of endocytosed midkine, a heparin-binding growth factor, was suppressed by both proteasome and lysosome inhibitors to similar extents. By contrast, a proteasome inhibitor, but not lysosome ones, accelerated the nuclear accumulation of midkine. An expression vector of signal sequence-less midkine, which is produced in the cytosol, was constructed because endocytosed midkine may be translocated to the cytosol from cellular compartments before entering the nucleus. The cytosol-produced midkine underwent proteasomal degradation and accumulated in the nucleus as did the endocytosed midkine. It was polyubiquitinated, and its nuclear accumulation was enhanced by a proteasome inhibitor. We further dissected the midkine molecule to investigate roles in degradation and trafficking. The N-terminal half-domain of midkine was significantly more susceptible to proteasomal degradation, whereas the C-terminal half-domain was sufficient for nuclear localization. Together, these data highlight the desensitization of nuclear targeting by growth factors and indicate a critical role of the proteasome system in it.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17785-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14970216-Animals, pubmed-meshheading:14970216-COS Cells, pubmed-meshheading:14970216-Carrier Proteins, pubmed-meshheading:14970216-Cell Nucleus, pubmed-meshheading:14970216-Cells, Cultured, pubmed-meshheading:14970216-Cysteine Endopeptidases, pubmed-meshheading:14970216-Cytokines, pubmed-meshheading:14970216-Cytosol, pubmed-meshheading:14970216-Endocytosis, pubmed-meshheading:14970216-Fibroblasts, pubmed-meshheading:14970216-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:14970216-Growth Substances, pubmed-meshheading:14970216-Humans, pubmed-meshheading:14970216-Kinetics, pubmed-meshheading:14970216-Lysosomes, pubmed-meshheading:14970216-Mice, pubmed-meshheading:14970216-Multienzyme Complexes, pubmed-meshheading:14970216-Plasmids, pubmed-meshheading:14970216-Proteasome Endopeptidase Complex, pubmed-meshheading:14970216-Protein Structure, Tertiary, pubmed-meshheading:14970216-Signal Transduction, pubmed-meshheading:14970216-Time Factors, pubmed-meshheading:14970216-Transfection, pubmed-meshheading:14970216-Ubiquitin
pubmed:year
2004
pubmed:articleTitle
Proteasomal degradation of the nuclear targeting growth factor midkine.
pubmed:affiliation
Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't