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 SCFβ-TrCP1 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.