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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Novel p104 protein regulates cell proliferation through PI3K inhibition and p27Kip1 expression

  • Han, Seung-Jin (School of Biological Sciences, Inje University) ;
  • Lee, Jung-Hyun (Institute of Molecular Biology and Genetics, Seoul National University) ;
  • Choi, Ki-Young (Institute of Molecular Biology and Genetics, Seoul National University) ;
  • Hong, Seung-Hwan (Institute of Molecular Biology and Genetics, Seoul National University)
  • Published : 2010.03.31
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Abstract

The protein p104 was first isolated as a binding partner of the Src homology domain of phospholipase C$\gamma$1, and has been shown to associate with p85$\alpha$, Grb2. The ectopic expression of p104 reduced cellular growth rate, which was also achieved with the overexpression of only the proline-rich region of p104. The proline-rich region of p104 has been found to inhibit the colony formation of platelet-derived growth factor BB-stimulated NIH3T3 cells and MCF7 cancer cells on soft agar. Mutagenesis analysis showed that the second and third proline-rich regions are essential for growth control, as well as for interaction with p85$\alpha$. Overexpression of p104 increased the level of the cyclin-dependent kinase inhibitor, $p27^{Kip1}$, and inhibited the activity of phosphoinositide 3-kinase (PI3K). In summary, p104 interacts with p85$\alpha$ and is involved in the regulation of $p27^{Kip1}$ expression for the reduction of cellular proliferation.

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References

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