Nuclear translocation of upstream stimulating factor 2 (USF2) in activated mast cells: a possible role in their survival.
Multiple transcription factors are activated in the cytoplasm and translocated to the nucleus where they exert positive or negative control over cellular genes. Such subcellular traffic of transcription factors usually requires the presence of a positively charged nuclear localization sequence (NLS). Upstream stimulating factor 2 (USF2) is one of the few transcription factors that contain two potential domains for nuclear localization. In addition to the conventional basic NLS, USF2 contains a highly conserved USF-specific region that is involved in its nuclear translocation. In the present work, the induction of translocation of USF2 into the mast cell nucleus was observed and found to be dependent on activation of the cells either by IL-3 or IgE-Ag. It was also observed that the prevention of the translocation of USF2 to the nucleus, using a peptide derived from the specific USF-NLS region, significantly inhibited their IL-3-mediated survival. Thus, our findings show a direct connection between mast cell surface receptor-mediated USF2 nuclear translocation and cell viability.
Frenkel
S
S
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Kay
G
G
Nechushtan
H
H
Razin
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001854:Bone Marrow Cells; D002352:Carrier Proteins; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007106:Immune Sera / Q000494:pharmacology; D007377:Interleukin-3 / Q000037:antagonists & inhibitors / Q000502:physiology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011994:Recombinant Proteins; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051720:Upstream Stimulatory Factors
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D006131:Growth Inhibitors; D007106:Immune Sera; D007377:Interleukin-3; D019913:Nuclear Localization Signals; D010455:Peptides; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D014157:Transcription Factors; C114508:USF-NTI protein, synthetic; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; C497186:Usf2 protein, mouse; D005346:Fibroblast Growth Factors