Key result
Pin1 PPIase domain mutations compromise nuclear localization by disrupting interaction with Importin alpha5.
Why the study?
The regulatory mechanisms of Pin1 cellular localization, particularly its nuclear import, were not well understood.
This study identifies a novel nuclear localization signal in the PPIase domain of Pin1 that mediates its nuclear import via interaction with Importin alpha5.
Pin1 actively regulates diverse biological/pathological processes, but little is known about the regulatory mechanisms of its cellular localization. In this study, we report that the endogenous Pin1 is distributed in both nucleus and cytoplasm. We found that point mutations of several basic amino acids in the PPIase domain of Pin1 significantly compromise its nuclear localization. Such inhibition is independent of Pin1 enzymatic activity, and is mainly due to the defects in the nuclear import. A novel sequence harboring these residues was identified as a putative nuclear localization signal (NLS) of Pin1. Importin alpha5 of the nuclear import machinery was found to interact with Pin1.
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Lufei et al. (2008) studied this question. Point mutations in the PPIase domain of Pin1 vs. Wild-type/endogenous Pin1 was evaluated on Nuclear localization of Pin1. Point mutations of basic amino acids in the PPIase domain of Pin1 significantly compromise its nuclear localization by disrupting a novel nuclear localization signal that interacts with Importin alpha5.
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