This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xia, X.
Right arrow Articles by Hamburger, A. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xia, X.
Right arrow Articles by Hamburger, A. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2003, p. 1717-1725, Vol. 23, No. 5
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.5.1717-1725.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The N-Terminal 24 Amino Acids of the p55 Gamma Regulatory Subunit of Phosphoinositide 3-Kinase Binds Rb and Induces Cell Cycle Arrest

Xianmin Xia,1,{dagger} Aiwu Cheng,2,{ddagger} Damilola Akinmade,1,3 and Anne W. Hamburger1,3*

Greenebaum Cancer Center,1 Department of Physiology,2 Department of Pathology, University of Maryland, Baltimore, Maryland 212013

Received 13 September 2002/ Returned for modification 22 October 2002/ Accepted 6 December 2002

Although phosphoinositide 3-kinase (PI 3-kinase) is essential for cell cycle progression, the molecular mechanisms that regulate its diverse biological effects are poorly understood. We demonstrate here that Rb, a key regulator of cell cycle progression, associates with p55 kDa (p55{alpha} and p55{gamma}) regulatory subunits of PI 3-kinase in vivo and in vitro. Both confocal microscopy and biochemical analysis demonstrated the presence of p55{gamma} in the nucleus. The 24-amino-acid N-terminal end of p55{gamma}, which is unique among PI 3-kinase regulatory subunits, was sufficient to bind Rb. Addition of serum or growth factors to quiescent cells triggered the dissociation of Rb from p55. Ectopic expression of the 24-amino-acid N-terminal end of p55{gamma} inhibited cell cycle progression, as evidenced by induction of cell growth arrest at the G0/G1 phase, inhibition of DNA synthesis, inhibition of cyclin D and cyclin E promoter activity, and changes in the expression of cell cycle-related proteins. The inhibitory effects of the N-terminal end of p55{gamma} on cell cycle progression depended on the presence of functional Rb. These data demonstrate for the first time an association of p55{gamma} with Rb and show that modification of this association can lead to cell cycle arrest.

* Corresponding author. Mailing address: University of Maryland Greenebaum Cancer Center, 655 W. Baltimore St., Baltimore, MD 21201. Phone: (410) 328-3911. Fax: (410) 328-6559. E-mail: ahamburg{at}som.umaryland.edu.

{dagger} Present address: Protein Tech Group, Chicago, IL 60612.

{ddagger} Present address: Laboratory of Neuroscience, GRC, NIA, NIH, Baltimore, MD 21224.

Molecular and Cellular Biology, March 2003, p. 1717-1725, Vol. 23, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.5.1717-1725.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Acosta-Martinez, M., Luo, J., Elias, C., Wolfe, A., Levine, J. E. (2009). Male-Biased Effects of Gonadotropin-Releasing Hormone Neuron-Specific Deletion of the Phosphoinositide 3-Kinase Regulatory Subunit p85{alpha} on the Reproductive Axis. Endocrinology 150: 4203-4212 [Abstract] [Full Text]  
  • Hu, J., Xia, X., Cheng, A., Wang, G., Luo, X., Reed, M. F., Fojo, T., Oetting, A., Gong, J., Yen, P. M. (2008). A peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase regulatory subunit: a novel cancer therapy. Molecular Cancer Therapeutics 7: 3719-3728 [Abstract] [Full Text]  
  • Eiring, A. M., Neviani, P., Santhanam, R., Oaks, J. J., Chang, J. S., Notari, M., Willis, W., Gambacorti-Passerini, C., Volinia, S., Marcucci, G., Caligiuri, M. A., Leone, G. W., Perrotti, D. (2008). Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood 111: 816-828 [Abstract] [Full Text]  
  • Kallin, A., Johannessen, L. E., Cani, P. D., Marbehant, C. Y., Essaghir, A., Foufelle, F., Ferre, P., Heldin, C.-H., Delzenne, N. M., Demoulin, J.-B. (2007). SREBP-1 regulates the expression of heme oxygenase 1 and the phosphatidylinositol-3 kinase regulatory subunit p55{gamma}. J. Lipid Res. 48: 1628-1636 [Abstract] [Full Text]  
  • Deane, J. A., Kharas, M. G., Oak, J. S., Stiles, L. N., Luo, J., Moore, T. I., Ji, H., Rommel, C., Cantley, L. C., Lane, T. E., Fruman, D. A. (2007). T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling. Blood 109: 2894-2902 [Abstract] [Full Text]  
  • Carney, S. A., Chen, J., Burns, C. G., Xiong, K. M., Peterson, R. E., Heideman, W. (2006). Aryl Hydrocarbon Receptor Activation Produces Heart-Specific Transcriptional and Toxic Responses in Developing Zebrafish. Mol. Pharmacol. 70: 549-561 [Abstract] [Full Text]  
  • Aaboe, M., Birkenkamp-Demtroder, K., Wiuf, C., Sorensen, F. B., Thykjaer, T., Sauter, G., Jensen, K. M.-E., Dyrskjot, L., Orntoft, T. (2006). SOX4 Expression in Bladder Carcinoma: Clinical Aspects and In vitro Functional Characterization.. Cancer Res. 66: 3434-3442 [Abstract] [Full Text]  
  • Los, A. P., Vinke, F. P., de Widt, J., Topham, M. K., van Blitterswijk, W. J., Divecha, N. (2006). The Retinoblastoma Family Proteins Bind to and Activate Diacylglycerol Kinase{zeta}. J. Biol. Chem. 281: 858-866 [Abstract] [Full Text]  
  • Mallory, J. C., Crudden, G., Oliva, A., Saunders, C., Stromberg, A., Craven, R. J. (2005). A Novel Group of Genes Regulates Susceptibility to Antineoplastic Drugs in Highly Tumorigenic Breast Cancer Cells. Mol. Pharmacol. 68: 1747-1756 [Abstract] [Full Text]  
  • Brachmann, S. M., Yballe, C. M., Innocenti, M., Deane, J. A., Fruman, D. A., Thomas, S. M., Cantley, L. C. (2005). Role of Phosphoinositide 3-Kinase Regulatory Isoforms in Development and Actin Rearrangement. Mol. Cell. Biol. 25: 2593-2606 [Abstract] [Full Text]  
  • Chen, D., Mauvais-Jarvis, F., Bluher, M., Fisher, S. J., Jozsi, A., Goodyear, L. J., Ueki, K., Kahn, C. R. (2004). p50{alpha}/p55{alpha} Phosphoinositide 3-Kinase Knockout Mice Exhibit Enhanced Insulin Sensitivity. Mol. Cell. Biol. 24: 320-329 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»