Centromere protein W interacts with beta-transducin repeat-containing protein 1 and modulates its subcellular localization.

Beta-transducin repeat-containing protein 1 (β-TrCP1) is a substrate-recognition module of SCF ubiquitin ligases and its subcellular distribution is known to be critical for target specificity. Heterogeneous nuclear ribonucleoprotein (hnRNP) U, an abundant nuclear protein, is known to be a unique regulator of β-TrCP1 shuttling between the cytoplasm and the nucleus. In this study, we report that centromere protein W (CENP-W), which is frequently overexpressed in a variety of human cancers, may also contribute to β-TrCP1 shuttling. Although hnRNP U and CENP-W can interact with β-TrCP1 and transport it independently, these proteins do not compete for β-TrCP1 binding, but rather cooperate to form a stable shuttling complex. Intriguingly, we found that overexpression of CENP-W leads to accumulation of β-TrCP1 in the nucleus. Thus, we propose that CENP-W may function as a booster of β-TrCP1 nuclear import to increase the oncogenicity of β-TrCP1.