Stat3-dependent induction of BATF in M1 mouse myeloid leukemia cells.
Stat3 mediates cellular responses associated with proliferation, survival and differentiation, but the mechanisms underlying the diverse effects of this signaling molecule remain unknown. M1 mouse myeloid leukemia cells arrest growth and differentiate into macrophages following treatment with interleukin 6 (IL-6) or leukemia inhibitory factor (LIF), and recent studies have shown that Stat3 plays a central role in this process. Utilizing representational difference analysis, we demonstrate that expression of the mouse BATF gene is upregulated as an early response to IL-6/LIF stimulation and Stat3 activation in this cell system. Immunoblots using antibodies to BATF detected an increase in BATF protein in response to LIF/IL-6 stimulation. BATF is a member of the AP-1 family of basic leucine zipper transcription factors and functions to inhibit the transcriptional and biological functions of AP-1 activity in mammalian cells. BATF forms complexes with c-Jun in M1 cells and forced expression of BATF in the absence of Stat3 signaling results in a reduced rate of cellular growth. These results indicate that Stat3 mediates cellular growth by modulating AP-1 activity through the induction of BATF.
Senga
Takeshi
T
Department of Molecular Pathogenesis, Nagoya University School of Medicine, 65 Tsurumai Showa Nagoya 466-8550, Japan.
Iwamoto
Takashi
T
Humphrey
Sean E
SE
Yokota
Takashi
T
Taparowsky
Elizabeth J
EJ
Hamaguchi
Michinari
M
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D006131:Growth Inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016350:Leucine Zippers; D053605:Leukemia Inhibitory Factor; D007951:Leukemia, Myeloid / Q000473:pathology*; D008222:Lymphokines / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one