Nuclear import of Pin1 is mediated by a novel sequence in the PPIase domain.
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.
Lufei
Chengchen
C
Institute of Molecular and Cell Biology, A *STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Biopolis, Singapore 138673, Republic of Singapore.
Cao
Xinmin
X
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology*; D003593:Cytoplasm / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism; D000097606:Exportin 1 Protein
D001120:Arginine; D028884:Karyopherins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019913:Nuclear Localization Signals; D019696:Peptidylprolyl Isomerase; D018160:Receptors, Cytoplasmic and Nuclear; D028901:alpha Karyopherins; D000097606:Exportin 1 Protein; C423142:KPNA1 protein, human; C000606846:PIN1 protein, human