Editors' ChoiceBiochemistry

PIKing Oncogenic Mutations

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Science's STKE  18 Dec 2007:
Vol. 2007, Issue 417, pp. tw457
DOI: 10.1126/stke.4172007tw457

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that can initiate a variety of signaling events. Many human cancers involve mutations that activate PI3Kα, a heterodimer composed of a catalytic subunit, p110α, and a regulatory subunit, p85α, both of which contain multiple domains. Huang et al. describe the crystal structure of a complex between the full-length human p110α catalytic subunit and the binding and activation domains of the p85α regulatory subunit. The structure provides insight into how oncogenic mutations affect enzyme activity and could assist in the future design of isoform- or mutation-specific inhibitors.

C.-H. Huang, D. Mandelker, O. Schmidt-Kittler, Y. Samuels, V. E. Velculescu, K. W. Kinzler, B. Vogelstein, S. B. Gabelli, L. M. Amzel, The structure of a human p110α/p85α complex elucidates the effects of oncogenic PI3Kα mutations. Science 318, 1744-1748 (2007). [Abstract] [Full Text]

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