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:

PPARγ controls cell proliferation and apoptosis in an RB-dependent manner

Abstract

The nuclear receptor PPARγ is implicated in the control of cell proliferation and apoptosis. However, the molecular mechanisms by which it controls these processes remain largely elusive. We show here that PPARγ activation in the presence of the retinoblastoma protein (RB) results in the arrest of cells at the G1 phase of the cell cycle, whereas in the absence of RB, cells accumulate in G2/M, endoreduplicate, and undergo apoptosis. Through the use of HDAC inhibitors and coimmunoprecipitations, we furthermore demonstrate that the effects of RB on PPARγ-mediated control of the cell cycle and apoptosis depend on the recruitment of histone deacetylase 3 (HDAC3) to PPARγ. In combination, these data hence demonstrate that the effects of PPARγ on cell proliferation and apoptosis are dependent on the presence of an RB–HDAC3 complex.

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

  • Altiok S, Xu M and Spiegelman B . (1997). Gen. Dev., 11, 1987–1998.

  • Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ and Kouzarides T . (1998). Nature, 391, 597–601.

  • Chang BD, Broude EV, Fang J, Kalinichenko TV, Abdryashitov R, Poole JC and Roninson IB . (2000). Oncogene, 19, 2165–2170.

  • Chang TH and Szabo E . (2000). Cancer Res., 60, 1129–1138.

  • Chang TH and Szabo E . (2002). Clin. Cancer Res., 8, 1206–1212.

  • Clarke AR, Maandag ER, van Roon M, van der Lugt NM, van der Valk M, Hooper ML, Berns A and te Riele H . (1992). Nature, 359, 328–330.

  • Elstner E, Muller C, Koshizuka K, Williamson EA, Park D, Asou H, Shintaku P, Said JW, Heber D and Koeffler HP . (1998). Proc. Nat. Acad. Sci. USA, 95, 8806–8811.

  • Fajas L, Auboeuf D, Raspe E, Schoonjans K, Lefebvre AM, Saladin R, Najib J, Laville M, Fruchart JC, Deeb S, Vidal-Puig A, Flier J, Briggs MR, Staels B, Vidal H and Auwerx J . (1997). J. Biol. Chem., 272, 18779–18789.

  • Fajas L, Debril MB and Auwerx J . (2001). J. Mol. Endocrinol., 27, 1–9.

  • Fajas L, Egler V, Reiter R, Hansen J, Kristiansen K, Miard S and Auwerx J . (2002). Dev. Cell, 3, 903–910.

  • Fajas L, Paul C, Zugasti O, Le Cam L, Polanowska J, Fabbrizio E, Medema R, Vignais ML and Sardet C . (2000). Proc. Natl. Acad. Sci. USA, 97, 7738–7743.

  • Guy M, Moorghen M, Bond JA, Collard TJ, Paraskeva C and Williams AC . (2001). Br. J. Cancer, 84, 520–528.

  • Hatakeyama M and Weinberg RA . (1995). Prog. Cell Cycle Res., 1, 9–19.

  • Helin K . (1998). Curr. Opin. Genet. Dev., 8, 28–35.

  • Koga H, Sakisaka S, Harada M, Takagi T, Hanada S, Taniguchi E, Kawaguchi T, Sasatomi K, Kimura R, Hashimoto O, Ueno T, Yano H, Kojiro M and Sata M . (2001). Hepatology, 33, 1087–1097.

  • Lefebvre A, Chen I, Desreumaux P, Najib J, Fruchart J, Geboes K, Briggs M, Heyman R and Auwerx J . (1998). Nat. Med., 4, 1053–1057.

  • Lefebvre AM, Paulweber B, Fajas L, Woods J, McCrary C, Colombel J-F, Najib J, Fruchart J-C, Datz C, Vidal H, Desreumaux P and Auwerx J . (1999). J. Endocrinol., 162, 331–340.

  • Magnaghi-Jaulin L, Groisman R, Naguibneva L, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D and Harel-Bellan A . (1998). Nature, 391, 601–605.

  • Morgenbesser SD, Williams BO, Jacks T and DePinho RA . (1994). Nature, 371, 72–74.

  • Morrison RF and Farmer SR . (1999). J. Biol. Chem., 274, 17088–17097.

  • Niculescu III AB, Chen X, Smeets M, Hengst L, Prives C and Reed SI . (1998). Mol. Cell. Biol., 18, 629–643.

  • Padilla J, Kaur K, Cao HJ, Smith TJ and Phipps RP . (2000). J. Immunol., 165, 6941–6948.

  • Palakurthi SS, Aktas H, Grubissich LM, Mortensen RM and Halperin JA . (2001). Cancer Res., 61, 6213–6218.

  • Pan H and Griep AE . (1995). Genes Dev., 9, 2157–2169.

  • Rocchi S, Picard F, Vamecq J, Gelman L, Potier N, Zeyer D, Dubuquoy L, Bac P, Champy MF, Plunket KD, Leesnitzer LM, Blanchard SG, Desreumaux P, Moras D, Renaud JP and Auwerx J . (2001). Mol. Cell, 8, 737–747.

  • Rosen ED, Walkey CJ, Puigserver P and Spiegelman BM . (2000). Genes Dev., 14, 1293–1307.

  • Saez E, Tontonoz P, Nelson MC, Alvarez JGA, Ming UT, Baird SM, Thomazy VA and Evans RM . (1998). Nat. Med., 4, 1058–1061.

  • Tsai KY, Hu Y, Macleod KF, Crowley D, Yamasaki L and Jacks T . (1998). Mol. Cell, 2, 293–304.

  • Wakino S, Kintscher U, Kim S, Yin F, Hsueh WA and Law RE . (2000). J. Biol. Chem., 275, 22435–22441.

  • Wang C, Fu M, D'Amico M, Albanese C, Zhou JN, Brownlee M, Lisanti MP, Chatterjee VK, Lazar MA and Pestell RG . (2001). Mol. Cell. Biol., 21, 3057–3070.

  • Yamamoto H, Soh JW, Monden T, Klein MG, Zhang LM, Shirin H, Arber N, Tomita N, Schieren I, Stein CA and Weinstein IB . (1999). Clin. Cancer Res., 5, 1805–1815.

Download references

Acknowledgements

J-M Blanchard, C Sardet, and R Heyman are acknowledged for the gift of materials, and P Chambon, A Gandarillas, and the Auwerx lab for support and discussion. This work was supported by grants of CNRS, INSERM, Hôpital Universitaire de Strasbourg, ARC (#5800, #4724), the NIH Program project (1 P01-DK59820-01), and the European community RTD program (QLG1-CT-1999-00674).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Johan Auwerx.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fajas, L., Egler, V., Reiter, R. et al. PPARγ controls cell proliferation and apoptosis in an RB-dependent manner. Oncogene 22, 4186–4193 (2003). https://doi.org/10.1038/sj.onc.1206530

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206530

Keywords

This article is cited by

Search

Quick links