Profilin regulates the activity of p42^POP, a novel Myb-related transcription factor

Profilins, regulators of cytoplasmic actin dynamics, also bind to several nuclear proteins but the significance of these interactions is mostly unclear. Here, we describe a novel Myb-related transcription factor, p42^POP, as a new ligand for profilin and show that profilin regulates its activity. p42^POP comprises a unique combination of domains and is widely expressed in mouse tissues. In contrast to many other Myb proteins, it contains only one functional tryptophan-cluster motif. This is followed by an acidic domain, a leucine zipper that mediates dimerization and functional nuclear import and export signals that can direct p42^POP to either the nuclear or the cytoplasmic compartment. Binding to profilins is mediated by a proline-rich cluster. p42^POP-profilin complexes can be precipitated from cell lysates. In transfected cells displaying p42^POP in the nucleus, nuclear profilin is markedly increased. When p42^POP is anchored at mitochondrial membranes, profilin is targeted to this location. Hence, in a cellular environment, p42^POP and profilin are found in the same protein complex. In luciferase assays, p42^POP acts as repressor and this activity is substantially reduced by profilins, indicating that profilin can regulate p42^POP activity and is therefore involved in gene regulation.