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Stat1 nuclear translocation by nucleolin upon monocyte differentiation

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Item Type:Article
Title:Stat1 nuclear translocation by nucleolin upon monocyte differentiation
Creators Name:Jerke, U. and Tkachuk, S. and Kiyan, J. and Stepanova, V. and Kusch, A. and Hinz, M. and Dietz, R. and Haller, H. and Fuhrman, B. and Dumler, I.
Abstract:BACKGROUND: Members of the signal transducer and activator of transcription (Stat) family of transcription factors traverse the nuclear membrane through a specialized structure, called the nuclear pore complex (NPC), which represents a selective filter for the import of proteins. Karyophilic molecules can bind directly to a subset of proteins of the NPC, collectively called nucleoporins. Alternatively, the transport is mediated via a carrier molecule belonging to the importin/karyopherin superfamily, which transmits the import into the nucleus through the NPC. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we provide evidence for an alternative Stat1 nuclear import mechanism, which is mediated by the shuttle protein nucleolin. We observed Stat1-nucleolin association, nuclear translocation and specific binding to the regulatory DNA element GAS. Using expression of nucleolin transgenes, we found that the nuclear localization signal (NLS) of nucleolin is responsible for Stat1 nuclear translocation. We show that this mechanism is utilized upon differentiation of myeloid cells and is specific for the differentiation step from monocytes to macrophages. CONCLUSIONS/SIGNIFICANCE: Our data add the nucleolin-Stat1 complex as a novel functional partner for the cell differentiation program, which is uniquely poised to regulate the transcription machinery via Stat1 and nuclear metabolism via nucleolin.
Keywords:Cell Nucleus Active Transport, CD36 Antigens, Base Sequence, Cell Differentiation, Cell Line, Cell Nucleus, Gene Silencing, Macrophages, Monocytes, Nuclear Localization Signals, Phosphoproteins, Protein Binding, RNA-Binding Proteins, STAT1 Transcription Factor, Structure-Activity Relationship, Time Factors, Animals, Mice
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science
Volume:4
Number:12
Page Range:e8302
Date:14 December 2009
Official Publication:https://doi.org/10.1371/journal.pone.0008302
PubMed:View item in PubMed

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