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Cell cycle

Akt Skps through

Nature Reviews Cancer volume 9, pages 316–317 (2009)Cite this article

SKP2 is known to be phosphorylated at the G1/S transition of the cell cycle, but the importance of this modification was not clear. Lin et al. found that Akt phosphorylated SKP2 at serine 72 in vivo, which increased SCF complex formation and promoted the ubiquitylation and degradation of p27. Expression of wild-type or phosphomimetic, but not phosphorylation-deficient, SKP2 also increased the proliferation and tumorigenic potential of a prostate cancer cell line.

Gao et al. showed that inhibition of PI3K–Akt signalling decreased SKP2 expression and confirmed that SKP2 was a direct substrate of AKT1, but not AKT2. Interestingly, Akt-mediated phosphorylation of SKP2 at serine 72 stimulated subsequent phosphorylation at serine 75 by casein kinase I. It was known that the E3 ubiquitin ligase complex APC–CDH1 mediates SKP2 destruction, and phosphorylation at both these residues inhibited its interaction with CDH1.

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References

ORIGINAL RESEARCH PAPER

  1. Lin, H.-K. et al. Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB Nature Cell Biol. 8 Mar 2009 (doi: 10.1038/ncb1849)

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  2. Gao, D. et al. Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APC–Cdh1-mediated Skp2 destruction Nature Cell Biol. 8 Mar 2009 (doi 10.1038/ncb1847)

FURTHER READING

  1. Frecas, D. & Pagano, M. Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer. Nature Rev. Cancer 8, 438–449 (2008).

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Authors and Affiliations

  1. UCSD–Nature Signaling Gateway,

    Emily J. Chenette

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  1. Emily J. Chenette
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Chenette, E. Akt Skps through. Nat Rev Cancer 9, 316–317 (2009). https://doi.org/10.1038/nrc2649

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  • DOI: https://doi.org/10.1038/nrc2649

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