Stat1 nuclear translocation by nucleolin upon monocyte differentiation.
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.


RESULTS
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
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.
Jerke
Uwe
U
Hannover Medical School, Hannover, Germany. uwe.jerke@charite.de
Tkachuk
Sergey
S
Kiyan
Julia
J
Stepanova
Victoria
V
Kusch
Angelika
A
Hinz
Michael
M
Dietz
Rainer
R
Haller
Hermann
H
Fuhrman
Bianca
B
Dumler
Inna
I
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001483:Base Sequence; D018955:CD36 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors; D000097796:Nucleolin
D018955:CD36 Antigens; D019913:Nuclear Localization Signals; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor; D000097796:Nucleolin; C494079:STAT1 protein, human