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14‐3‐3 suppresses the nuclear localization of threonine 157‐phosphorylated p27 Kip1
Author(s) -
Sekimoto Toshihiro,
Fukumoto Masahiro,
Yoneda Yoshihiro
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600198
Subject(s) - frontier , graduate students , library science , humanities , psychology , medicine , geography , medical education , art , computer science , archaeology
p27 Kip1 (p27), a CDK inhibitor, migrates into the nucleus, where it controls cyclin–CDK complex activity for proper cell cycle progression. We report here that the classical bipartite‐type basic amino‐acid cluster and the two downstream amino acids of the C‐terminal region of p27 function as a nuclear localization signal (NLS) for its full nuclear import activity. Importin α3 and α5, but not α1, transported p27 into the nucleus in conjunction with importin β, as evidenced by an in vitro transport assay. It is known that Akt phosphorylates Thr 157 of p27 and this reduces the nuclear import activity of p27. Using a pull‐down experiment, 14‐3‐3 was identified as the Thr157‐phosphorylated p27NLS‐binding protein. Although importin α5 bound to Thr157‐phosphorylated p27NLS, 14‐3‐3 competed with importin α5 for binding to it. Thus, 14‐3‐3 sequestered phosphorylated p27NLS from importin α binding, resulting in cytoplasmic localization of NLS‐phosphorylated p27. These findings indicate that 14‐3‐3 suppresses importin α/β‐dependent nuclear localization of Thr157‐phosphorylated p27, suggesting implications for cell cycle disorder in Akt‐activated cancer cells.