Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Modulation of specific protein expression levels by PTEN: identification of AKAP121, DHFR, G3BP, Rap1 and RCC1 as potential targets of PTEN

Abstract

The tumor suppressor PTEN is mutated in a high percentage of human cancers and is implicated in pathways regulating cell growth, proliferation, survival and migration. Despite significant advances, our understanding of its mechanisms of action remains incomplete. We have used a high-throughput proteomic immunoblotting approach to identify proteins whose expression levels are modulated by PTEN. Out of over 800 proteins screened, 22 proteins showed significant changes in expression. Five proteins that exhibited two-fold or greater changes in expression level were further characterized. AKAP121 and G3BP expression was reduced, while dihydrofolate reductase (DHFR), Rap1 and RCC1 expression was elevated in response to PTEN expression in a PTEN-null T-cell leukemia line. The phosphatase activity of PTEN was required for these effects. However, direct inhibition of PI-3 Kinase could mimic PTEN in modulating expression of DHFR, G3BP, Rap1 and RCC1, but not AKAP121. Real-time PCR showed that the effects of PTEN were primarily post-transcriptional and would not have been revealed by mRNA-based screens. We conclude from these data that PTEN can modulate the expression level of a number of different proteins. The identified proteins have the potential to serve as previously unrecognized effectors of PTEN and suggest the existence of additional complexity in the modes by which PTEN can regulate cellular biology.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Costa M, Ochem A, Staub A and Falaschi A . (1999). Nucleic Acids Res., 27, 817–821.

  • Davies SP, Reddy H, Caivano M and Cohen P . (2000). Biochem. J., 351, 95–105.

  • Di Cristofano A, Kotsi P, Peng YF, Cordon-Cardo C, Elkon KB and Pandolfi PP . (1999). Science, 285, 2122–2125.

  • Di Cristofano A, Pesce B, Cordon-Cardo C and Pandolfi PP . (1998). Nat. Genet., 19, 348–355.

  • Downward J . (2004). Semin. Cell Dev. Biol., 15, 177–182.

  • Furnari FB, Huang HJ and Cavenee WK . (1998). Cancer Res., 58, 5002–5008.

  • Gallouzi IE, Parker F, Chebli K, Maurier F, Labourier E, Barlat I, Capony JP, Tocque B and Tazi J . (1998). Mol. Cell Biol., 18, 3956–3965.

  • Guitard E, Parker F, Millon R, Abecassis J and Tocque B . (2001). Cancer Lett., 162, 213–221.

  • Jope RS and Johnson GV . (2004). Trends Biochem. Sci., 29, 95–102.

  • Kociok N, Esser P, Unfried K, Parker F, Schraermeyer U, Grisanti S, Toque B and Heimann K . (1999). J. Cell Biochem., 74, 194–201.

  • Li DM and Sun H . (1997). Cancer Res., 57, 2124–2129.

  • Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH and Parsons R . (1997). Science, 275, 1943–1947.

  • Liu K, Li Y, Prabhu V, Young L, Becker KG, Munson PJ and Weng N . (2001). J. Immunol., 166, 7335–7344.

  • Livak KJ . (2004). User Bulletin No. 2. PE Applied Biosystems.

  • Maehama T and Dixon JE . (1998). J. Biol. Chem., 273, 13375–13378.

  • Mahimainathan L and Choudhury GG . (2004). J. Biol. Chem., 279, 15258–15268.

  • Mamillapalli R, Gavrilova N, Mihaylova VT, Tsvetkov LM, Wu H, Zhang H and Sun H . (2001). Curr. Biol., 11, 263–267.

  • Moore JD . (2001). BioEssays, 23, 77–85.

  • Myers MP, Pass I, Batty IH, Van der KJ, Stolarov JP, Hemmings BA, Wigler MH, Downes CP and Tonks NK . (1998). Proc. Natl. Acad. Sci. USA, 95, 13513–13518.

  • Myers MP, Stolarov JP, Eng C, Li J, Wang SI, Wigler MH, Parsons R and Tonks NK . (1997). Proc. Natl. Acad. Sci. USA, 94, 9052–9057.

  • Parker F, Maurier F, Delumeau I, Duchesne M, Faucher D, Debussche L, Dugue A, Schweighoffer F and Tocque B . (1996). Mol. Cell Biol., 16, 2561–2569.

  • Pazman C, Mayes CA, Fanto M, Haynes SR and Mlodzik M . (2000). Development, 127, 1715–1725.

  • Pilarski R and Eng C . (2004). J. Med. Genet., 41, 323–326.

  • Pinna LA . (2002). J. Cell Sci., 115, 3873–3878.

  • Plas DR and Thompson CB . (2003). J. Biol. Chem., 278, 12361–12366.

  • Powis G, Bonjouklian R, Berggren MM, Gallegos A, Abraham R, Ashendel C, Zalkow L, Matter WF, Dodge J and Grindey G . (1994). Cancer Res., 54, 2419–2423.

  • Raftopoulou M, Etienne-Manneville S, Self A, Nicholls S and Hall A . (2004). Science, 303, 1179–1181.

  • Ramaswamy S, Nakamura N, Vazquez F, Batt DB, Perera S, Roberts TM and Sellers WR . (1999). Proc. Natl. Acad. Sci. USA., 96, 2110–2115.

  • Reed SI . (2003). Nat. Rev. Mol. Cell Biol., 4, 855–864.

  • Richardson CJ, Schalm SS and Blenis J . (2004). Semin. Cell Dev. Biol., 15, 147–159.

  • Sakai A, Thieblemont C, Wellmann A, Jaffe ES and Raffeld M . (1998). Blood, 92, 3410–3415.

  • Schneider U, Schwenk HU and Bornkamm G . (1977). Int. J. Cancer, 19, 621–626.

  • Seminario MC, Precht P, Wersto RP, Gorospe M and Wange RL . (2003). Oncogene, 22, 8195–8204.

  • Shan X, Czar MJ, Bunnell SC, Liu P, Liu Y, Schwartzberg PL and Wange RL . (2000). Mol. Cell Biol., 20, 6945–6957.

  • Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH and Tavtigian SV . (1997). Nat. Genet., 15, 356–362.

  • Sulis ML and Parsons R . (2003). Trends Cell Biol., 13, 478–483.

  • Tamura M, Gu J, Tran H and Yamada KM . (1999). J. Natl. Cancer Inst., 91, 1820–1828.

  • Tourriere H, Gallouzi IE, Chebli K, Capony JP, Mouaikel J, van der GP and Tazi J . (2001). Mol. Cell Biol., 21, 7747–7760.

  • Waite KA and Eng C . (2002). Am. J. Hum. Genet., 70, 829–844.

  • Wange RL, Isakov N, Burke Jr. TR, Otaka A, Roller PP, Watts JD, Aebersold R and Samelson LE . (1995). J. Biol. Chem., 270, 944–948.

  • Weng NP, Levine BL, June CH and Hodes RJ . (1995). Proc. Natl. Acad. Sci. USA, 92, 11091–11094.

  • Xu Z, Stokoe D, Kane LP and Weiss A . (2002). Cell Growth Differ., 13, 285–296.

  • Yamaguchi R and Newport J . (2003). Cell, 113, 115–125.

Download references

Acknowledgements

We thank Dr P Morin for his help with the real-time PCR analysis and for his many useful comments, Dr J Tazi for G3BP cDNA, Drs NP Weng, D Taub, Y Yang, M Fann and A Lustig for their various contributions towards the [3H]thymidine uptake assay and the purification of CD4+ T cells.

Author information

Authors and Affiliations

Authors

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, Y., Wernyj, R., Norton, D. et al. Modulation of specific protein expression levels by PTEN: identification of AKAP121, DHFR, G3BP, Rap1 and RCC1 as potential targets of PTEN. Oncogene 24, 3819–3829 (2005). https://doi.org/10.1038/sj.onc.1208527

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208527

Keywords

This article is cited by

Search

Quick links