Abstract
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.