Gene interactions and pathways from curated databases and text-mining
EMBO J 2004, PMID: 15057270

14-3-3 suppresses the nuclear localization of threonine 157-phosphorylated p27(Kip1).

Sekimoto, Toshihiro; Fukumoto, Masahiro; Yoneda, Yoshihiro

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 alpha3 and alpha5, but not alpha1, transported p27 into the nucleus in conjunction with importin beta, 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 alpha5 bound to Thr157-phosphorylated p27NLS, 14-3-3 competed with importin alpha5 for binding to it. Thus, 14-3-3 sequestered phosphorylated p27NLS from importin alpha binding, resulting in cytoplasmic localization of NLS-phosphorylated p27. These findings indicate that 14-3-3 suppresses importin alpha/beta-dependent nuclear localization of Thr157-phosphorylated p27, suggesting implications for cell cycle disorder in Akt-activated cancer cells.

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Text Mining Data

CDK ⊣ p27: " p27 ( Kip1 ) ( p27 ), a CDK inhibitor , migrates into the nucleus, where it controls cyclin-CDK complex activity for proper cell cycle progression "

Manually curated Databases

  • IRef Biogrid Interaction: CDKN1B — YWHAE (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CDKN1B — YWHAE (direct interaction, pull down)
  • IRef Biogrid Interaction: CDKN1B — YWHAB (direct interaction, pull down)
  • IRef Biogrid Interaction: CDKN1B — KPNA1 (direct interaction, pull down)
  • IRef Biogrid Interaction: CDKN1B — KPNA1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CDKN1B — KPNA1 (direct interaction, unspecified method)
  • IRef Biogrid Interaction: YWHAZ — CDKN1B (direct interaction, pull down)
  • IRef Biogrid Interaction: KPNA4 — CDKN1B (direct interaction, pull down)
  • IRef Hprd Interaction: CDKN1B — YWHAB (in vivo)
  • IRef Hprd Interaction: CDKN1B — YWHAB (in vitro)
  • IRef Hprd Interaction: CDKN1B — KPNA3 (in vitro)
  • IRef Hprd Interaction: CDKN1B — YWHAG (in vitro)
  • IRef Hprd Interaction: CDKN1B — YWHAG (in vivo)
  • IRef Hprd Interaction: CDKN1B — KPNA5 (in vitro)
  • IRef Intact Interaction: CDKN1B — YWHAE (physical association, pull down)
  • IRef Intact Interaction: Complex of CDKN1B-KPNA3 (association, pull down)
  • IRef Intact Interaction: CDKN1B — YWHAG (physical association, pull down)
  • IRef Intact Interaction: Complex of KPNA5-CDKN1B (association, pull down)
  • IRef Intact Interaction: CDKN1B — YWHAB (physical association, pull down)
  • IRef Intact Interaction: CDKN1B — KPNA3 (physical association, pull down)
  • IRef Intact Interaction: CDKN1B — KPNA5 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: CDKN1B — KPNA5 (physical association, pull down)
  • IRef Intact Interaction: Complex of RAN-KPNA5-CDKN1B-NUTF2-KPNA3 (physical association, biochemical)
  • IRef Intact Interaction: Complex of CDKN1B-RAN-NUTF2-KPNA3 (physical association, biochemical)
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: p27Kip1/14-3-3 family complex (CDKN1B-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB) → p27Kip1/KPNA1 complex (CDKN1B-KPNA1) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: p27Kip1/14-3-3 family complex (CDKN1B-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB) → KPNA1 (KPNA1) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: p27Kip1/14-3-3 family complex (CDKN1B-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB) → 14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: p27Kip1/14-3-3 family complex (CDKN1B-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB) → p27Kip1 (CDKN1B) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: p27Kip1/KPNA1 complex (CDKN1B-KPNA1) → KPNA1 (KPNA1) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: p27Kip1/KPNA1 complex (CDKN1B-KPNA1) → 14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: p27Kip1/KPNA1 complex (CDKN1B-KPNA1) → p27Kip1 (CDKN1B) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: KPNA1 (KPNA1) → 14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: KPNA1 (KPNA1) → p27Kip1 (CDKN1B) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database Class I PI3K signaling events mediated by Akt: 14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB) → p27Kip1 (CDKN1B) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
In total, 56 gene pairs are associated to this article in curated databases