Cellular localisation and nuclear export of the human bZIP transcription factor TCF11.
TCF11 is a ubiquitous transcription factor of the CNC-bZIP family. The activity of this vital protein is strictly regulated and we have previously published that the two major translated protein forms show a clearly different transactivation ability in transient transfections. Only the full-length form is active in a variety of mammalian cells [J. Biol. Chem. 276 (2001) 17641]. Here we further investigate the complex regulation of TCF11, studying the cellular localisation of some of the different protein isoforms. The full-length form is located both in the cytoplasm and the nucleus, while the internally initiated shorter protein form is restricted to nuclear localisation. A nuclear export signal (NES) localised in the N-terminus of TCF11 is responsible for the active nuclear export of the protein. This export is highly sensitive to leptomycin B (LMB) and is largely blocked by mutating three of the leucine residues in the signal region. These results indicate that export occurs through the Crm1-mediated pathway. Due to alternative splicing within the tcf11 gene, different isoforms of the longer protein form are produced. Some of these isoforms, one identical to Nrf1, lack the NES and are thereby restricted to nuclear localisation.
Biotechnology Centre of Oslo, University of Oslo, PB 1125 Blindern, Oslo 0316, Norway.
Cathrine
C
Husberg
Paula
P
Murphy
Elisa
E
Bjørgo
Karl-Henning
KH
Kalland
Anne-Brit
AB
Kolstø
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003593:Cytoplasm / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D051265:NF-E2-Related Factor 1; D019913:Nuclear Localization Signals; D021381:Protein Transport; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D051265:NF-E2-Related Factor 1; C088357:NFE2L1 protein, human; D019913:Nuclear Localization Signals; D014157:Transcription Factors; C038753:leptomycin B