title: Regulating inducible transcription through controlled localization.
abstract: Many signaling pathways regulate the activity of effector transcription factors by controlling their subcellular localization. Until recently, the cytoplasmic retention of inactive transcription factors was mainly attributed to binding partners that mask the nuclear localization signals (NLSs) of target proteins. Inactive transcription factors were thought to be exclusively cytoplasmic until their activation, after which the NLSs were unmasked to allow nuclear translocation. There is now a growing body of evidence, however, that challenges this simple model. This review discusses recent reports that suggest that inducible transcription factors can constantly shuttle between the cytoplasm and the nucleus, and that their apparent cytoplasmic retention can be achieved by binding partners that mask the NLSs, tether the transcription factor to cytoplasmic structures, or mark the transcription factor for proteasomal degradation. We also discuss the possibility that this more complex model of cytoplasmic retention might be applicable to a broader range of transcription factors and their associated signaling pathways.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Ziegler
authors.forename: Sankar
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D028884:Karyopherins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D000097606:Exportin 1 Protein
chemical_list: D005231:Fatty Acids, Unsaturated; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D016328:NF-kappa B; D046988:Proteasome Endopeptidase Complex; D018160:Receptors, Cytoplasmic and Nuclear; D051785:Smad Proteins; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C038753:leptomycin B