The POU protein Oct-6 is a nucleocytoplasmic shuttling protein.
Like many POU domain proteins, Oct-6 plays important roles during vertebrate development. In accord with its function as a transcriptional regulator during neurogenesis and myelination, Oct-6 is predominantly found in the nucleus. Nuclear import is mediated by a nuclear localization signal at the N-terminal end of the POU homeodomain. Here we show, that Oct-6 in addition contains a nuclear export signal so that Oct-6 is able to shuttle constantly between nucleus and cytoplasm. This nuclear export signal is also localized in the POU homeodomain as part of helix 2 and the connecting loop to DNA recognition helix 3. It conforms to the consensus of hydrophobic leucine-rich export sequences and mediates export from the nucleus via CRM1/Exp1. Several amino acid substitutions or insertions that inactivate this nuclear export sequence, reduce DNA-binding of Oct-6 to its octamer recognition element slighty, but interfere strongly with Oct-6-dependent transcriptional activation, thus arguing that nuclear export and nucleocytoplasmic shuttling are essential aspects of Oct-6 function. Importantly, the nuclear export signal identified for Oct-6 is conserved in most, if not all other vertebrate POU proteins. Nuclear export might therefore be of general relevance for POU protein function throughout development.
Baranek
Constanze
C
Institut für Biochemie, Universität Erlangen-Nürnberg D-91054 Erlangen, Germany.
Sock
Elisabeth
E
Wegner
Michael
M
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D007930:Leucine / Q000032:analysis; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015533:Transcriptional Activation; D000097606:Exportin 1 Protein
D028884:Karyopherins; D007930:Leucine; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein