STAT3beta does not interfere with granulocyte colony-stimulating factor-induced neutrophilic differentiation.
BACKGROUND
Activation of the signal transducer and activator of transcription protein STAT3 is a crucial step in granulocyte colony-stimulating factor (G-CSF)-mediated cell cycle exit and subsequent neutrophilic differentiation of myeloid precursor cells. We have recently demonstrated that this is mediated, at least in part, by upregulation of the cyclin-dependent kinase inhibitor p27(Kip1). The splice variant STAT3beta, that lacks a C-terminal serine residue implicated in the transcriptional activity of STAT3, has been shown to inhibit STAT3-mediated transcription in certain situations. STAT3beta is known to be expressed in hematopoietic cells, but its role in controlling the balance between proliferation and differentiation has not been established.


METHODS
We ectopically introduced STAT3beta in differentiation-competent 32D cell transfectants expressing human wild type (WT) G-CSF receptors and studied the consequences for G-CSF-mediated responses.


RESULTS
Overexpression of STAT3beta did not alter the kinetics of G-CSF-mediated neutrophilic differentiation or p27 induction in 32D/G-CSF-R WT cells. In addition, we found that p27(Kip1) promoter activity was not inhibited by STAT3beta, while inhibition of p27 transactivation by a dominant-negative STAT3 mutant could in fact be alleviated by coexpression of the beta form.


CONCLUSIONS
These findings argue against a role of STAT3beta as a negative regulator of G-CSF-induced expression of p27 and myeloid differentiation.
de Koning
J P
JP
Institute of Hematology, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Ward
A C
AC
Caldenhoven
E
E
de Groot
R P
RP
Löwenberg
B
B
Touw
I P
IP
D017398:Alternative Splicing; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000494:pharmacology / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D020033:Protein Isoforms; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D016179:Granulocyte Colony-Stimulating Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27