BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

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)
  • 발행 : 2010.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

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.

키워드

참고문헌

  1. Suh, P. G., Park, J. I., Manzoli, L., Cocco, L., Peak, J. C., Katan, M., Fukami, K., Kataoka, T., Yun, S. and Ryu, S. H. (2008) Multiple roles of phosphoinositide-specific phospholipase C isozymes. BMB Rep. 41, 415-434 https://doi.org/10.5483/BMBRep.2008.41.6.415
  2. Pawson, T. and Gish, G. D. (1992) SH2 and SH3 domains: from structure to function. Cell 71, 359-362 https://doi.org/10.1016/0092-8674(92)90504-6
  3. Roymans, D. and Slegers, H. (2001) Phosphatidylinositol 3-kinases in tumor progression. Eur. J. Biochem. 268, 487-498 https://doi.org/10.1046/j.1432-1327.2001.01936.x
  4. Luttrell, D. K., Lee, A., Lansing, T. J., Crosby, R. M., Jung, K. D., Willard, D., Luther, M., Rodriguez, M., Berman, J. and Gilmer, T. M. (1994) Involvement of pp60c-src with two major signaling pathways in human breast cancer. Proc. Natl. Acad. Sci. U.S.A. 91, 83-87 https://doi.org/10.1073/pnas.91.1.83
  5. Cussac, D., Vidal, M., Leprince, C., Liu, W. Q., Cornille, F., Tiraboschi, G., Roques, B. P. and Garbay, C. (1999) A Sos-derived peptidimer blocks the Ras signaling pathway by binding both Grb2 SH3 domains and displays antiproliferative activity. Faseb. J. 13, 31-38
  6. Smith, M. R., Liu, Y. L., Matthews, N. T., Rhee, S. G., Sung, W. K. and Kung, H. F. (1994) Phospholipase C-gamma 1 can induce DNA synthesis by a mechanism independent of its lipase activity. Proc. Natl. Acad. Sci. U.S.A. 91, 6554-6558 https://doi.org/10.1073/pnas.91.14.6554
  7. Polyak, K., Lee, M. H., Erdjument-Bromage, H., Koff, A., Roberts, J. M., Tempst, P. and Massague, J. (1994) Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 78, 59-66 https://doi.org/10.1016/0092-8674(94)90572-X
  8. Servant, M. J., Coulombe, P., Turgeon, B. and Meloche, S. (2000) Differential regulation of p27(Kip1) expression by mitogenic and hypertrophic factors: Involvement of transcriptional and posttranscriptional mechanisms. J. Cell Biol. 148, 543-556 https://doi.org/10.1083/jcb.148.3.543
  9. Starr, D. A. and Han, M. (2003) ANChors away: an actin based mechanism of nuclear positioning. J. Cell Sci. 116, 211-216 https://doi.org/10.1242/jcs.00248
  10. Han, S. J., Lee, J. H., Kim, C. G. and Hong, S. H. (2003) Identification of p115 as a PLCgamma1-binding protein and the role of Src homology domains of PLCgamma1 in the vesicular transport. Biochem. Biophys. Res. Commun. 300, 649-655 https://doi.org/10.1016/S0006-291X(02)02884-X
  11. Songyang, Z., Shoelson, S. E., Chaudhuri, M., Gish, G., Pawson, T., Haser, W. G., King, F., Roberts, T., Ratnofsky, S., Lechleider, R. J., Neel, B. G., Birge, R. B., Fajardo, J. E., Chou, M. M., Hanafusa, H., Schaffhausen, B. and Cantley, L. C. (1993) SH2 domains recognize specific phosphopeptide sequences. Cell 72, 767-778 https://doi.org/10.1016/0092-8674(93)90404-E
  12. Klippel, A., Reinhard, C., Kavanaugh, W. M., Apell, G., Escobedo, M. A. and Williams, L. T. (1996) Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways. Mol. Cell Biol. 16, 4117-4127 https://doi.org/10.1128/MCB.16.8.4117
  13. Collado, M., Medema, R. H., Garcia-Cao, I., Dubuisson, M. L., Barradas, M., Glassford, J., Rivas, C., Burgering, B. M., Serrano, M. and Lam, E. W. (2000) Inhibition of the phosphoinositide 3-kinase pathway induces a senescencelike arrest mediated by $p27^{Kip1}$. J. Biol. Chem. 275, 21960-21968 https://doi.org/10.1074/jbc.M000759200
  14. Medema, R. H., Kops, G. J., Bos, J. L. and Burgering, B. M. (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through $p27^{Kip1}$. Nature 404, 782-787 https://doi.org/10.1038/35008115
  15. Jeon, S. H., Kang, M. G., Kim, Y. H., Jin, Y. H., Lee, C., Chung, H. Y., Kwon, H., Park, S. D. and Seong, R. H. (1997) A new mouse gene, SRG3, related to the SWI3 of Saccharomyces cerevisiae, is required for apoptosis induced by glucocorticoids in a thymoma cell line. J. Exp. Med. 185, 1827-1836 https://doi.org/10.1084/jem.185.10.1827
  16. Kirchner, J. and Bevan, M. J. (1999) ITM2A is induced during thymocyte selection and T cell activation and causes downregulation of CD8 when overexpressed in CD4 (+)CD8(+) double positive thymocytes. J. Exp. Med. 190, 217-228 https://doi.org/10.1084/jem.190.2.217
  17. Vervoorts, J. and Luscher, B. (2008) Post-translational regulation of the tumor suppressor p27(KIP1). Cell Mol. Life Sci. 65, 3255-3264 https://doi.org/10.1007/s00018-008-8296-7
  18. Philipp-Staheli, J., Payne, S. R. and Kemp, C. J. (2001) p27(Kip1): regulation and function of a haploinsufficient tumor suppressor and its misregulation in cancer. Exp. Cell Res. 264, 148-168 https://doi.org/10.1006/excr.2000.5143

피인용 문헌

  1. Elevated RalA activity in the hippocampus of PI3Kγ knock-out mice lacking NMDAR-dependent long-term depression vol.46, pp.2, 2013, https://doi.org/10.5483/BMBRep.2013.46.2.143
  2. p104 Binds to Rac1 and Reduces Its Activity during Myotube Differentiation of C2C12 Cell vol.2014, 2014, https://doi.org/10.1155/2014/592450