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 Santoni-Rugiu, E.
Right arrow Articles by Lukas, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Santoni-Rugiu, E.
Right arrow Articles by Lukas, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2000, p. 3497-3509, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Involvement of Myc Activity in a G1/S-Promoting Mechanism Parallel to the pRb/E2F Pathway

Eric Santoni-Rugiu, Jacob Falck, Niels Mailand, Jiri Bartek,* and Jiri Lukas

Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen Ø., Denmark

Received 18 October 1999/Returned for modification 22 November 1999/Accepted 22 February 2000

The retinoblastoma protein (pRb)/E2F pathway regulates commitment of mammalian cells to replicate DNA. On the other hand, mitogen-stimulated cells deprived of E2F activity can still maintain physiologically relevant levels of cyclin E-dependent kinase activity and gradually enter S phase, suggesting the existence of a DNA synthesis-inducing mechanism parallel to the pRb/E2F axis. Here we show that regulatable ectopic expression of cyclin E or transcriptionally active Myc can rapidly induce DNA synthesis in U2OS-derived cell lines whose E2F activity is blocked by a constitutively active pRb (pRbDelta cdk) mutant. The effect of Myc is associated with Cdc25A phosphatase and cyclin E-CDK2 kinase activation and abolished by antagonizing Myc activity with the dominant-negative (dn) MadMyc chimera. Moreover, while abrogation of either endogenous E2F or Myc activity only delays and lowers DNA synthesis in synchronized U2OS cells or rat diploid fibroblasts, concomitant neutralization of both abolishes it. Whereas ectopic Myc and E2F1 rescue the G1/S delay caused by pRbDelta cdk (or dnDP1) and MadMyc, respectively, cyclin E or Cdc25A can restore DNA replication even in cells concomitantly exposed to pRbDelta cdk and MadMyc. However, coexpression of dnCDK2 neutralizes all of these rescuing effects. Finally, proper transcription of cyclin E and Cdc25A at the G1/S transition requires both Myc and E2F activities, and subthreshold levels of ectopic cyclin E and Cdc25A synergistically restore DNA synthesis in cells with silenced Myc and E2F activities. These results suggest that Myc controls a G1/S-promoting mechanism regulating cyclin E-CDK2 in parallel to the "classical" pRb/E2F pathway.

* Corresponding author. Mailing address: Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø., Denmark. Phone: 45 35 25 73 57. Fax: 45 35 25 77 21. E-mail: bartek{at}biobase.dk.

Molecular and Cellular Biology, May 2000, p. 3497-3509, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Esposito, F., Pierantoni, G. M., Battista, S., Melillo, R. M., Scala, S., Chieffi, P., Fedele, M., Fusco, A. (2009). Interaction between HMGA1 and Retinoblastoma Protein Is Required for Adipocyte Differentiation. J. Biol. Chem. 284: 25993-26004 [Abstract] [Full Text]  
  • Squires, M. S., Feltell, R. E., Wallis, N. G., Lewis, E. J., Smith, D.-M., Cross, D. M., Lyons, J. F., Thompson, N. T. (2009). Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Molecular Cancer Therapeutics 8: 324-332 [Abstract] [Full Text]  
  • Zheng, X., Rao, X.-M., Gomez-Gutierrez, J. G., Hao, H., McMasters, K. M., Zhou, H. S. (2008). Adenovirus E1B55K Region Is Required To Enhance Cyclin E Expression for Efficient Viral DNA Replication. J. Virol. 82: 3415-3427 [Abstract] [Full Text]  
  • Verykokakis, M., Papadaki, C., Vorgia, E., Le Gallic, L., Mavrothalassitis, G. (2007). The RAS-dependent ERF Control of Cell Proliferation and Differentiation Is Mediated by c-Myc Repression. J. Biol. Chem. 282: 30285-30294 [Abstract] [Full Text]  
  • Wen, R., Chen, Y., Bai, L., Fu, G., Schuman, J., Dai, X., Zeng, H., Yang, C., Stephan, R. P., Cleveland, J. L., Wang, D. (2006). Essential Role of Phospholipase C{gamma}2 in Early B-Cell Development and Myc-Mediated Lymphomagenesis. Mol. Cell. Biol. 26: 9364-9376 [Abstract] [Full Text]  
  • Simmons, D. P., Peach, M. L., Friedman, J. R., Green, M. M.B., Nicklaus, M. C., De Luca, L. M. (2006). Evidence that sequence homologous region in LRAT-like proteins possesses anti-proliferative activity and DNA binding properties: translational implications and mechanism of action. Carcinogenesis 27: 693-707 [Abstract] [Full Text]  
  • Dekanty, A., Sauane, M., Cadenas, B., Coluccio, F., Barrio, M., Casala, J., Paciencia, M., Rogers, F., Coso, O. A., Piwien-Pilipuk, G., Rudland, P. S., de Asua, L. J. (2006). Leukemia Inhibitory Factor Induces DNA Synthesis in Swiss Mouse 3T3 Cells Independently of Cyclin D1 Expression through a Mechanism Involving MEK/ERK1/2 Activation. J. Biol. Chem. 281: 6136-6143 [Abstract] [Full Text]  
  • Mukherjee, S., Conrad, S. E. (2005). c-Myc Suppresses p21WAF1/CIP1 Expression during Estrogen Signaling and Antiestrogen Resistance in Human Breast Cancer Cells. J. Biol. Chem. 280: 17617-17625 [Abstract] [Full Text]  
  • Barre, B., Vigneron, A., Coqueret, O. (2005). The STAT3 Transcription Factor Is a Target for the Myc and Riboblastoma Proteins on the Cdc25A Promoter. J. Biol. Chem. 280: 15673-15681 [Abstract] [Full Text]  
  • MacLellan, W. R., Garcia, A., Oh, H., Frenkel, P., Jordan, M. C., Roos, K. P., Schneider, M. D. (2005). Overlapping Roles of Pocket Proteins in the Myocardium Are Unmasked by Germ Line Deletion of p130 plus Heart-Specific Deletion of Rb. Mol. Cell. Biol. 25: 2486-2497 [Abstract] [Full Text]  
  • Rajabi, H. N., Baluchamy, S., Kolli, S., Nag, A., Srinivas, R., Raychaudhuri, P., Thimmapaya, B. (2005). Effects of Depletion of CREB-binding Protein on c-Myc Regulation and Cell Cycle G1-S Transition. J. Biol. Chem. 280: 361-374 [Abstract] [Full Text]  
  • Balmanno, K., Millar, T., McMahon, M., Cook, S. J. (2003). {Delta}Raf-1:ER* Bypasses the Cyclic AMP Block of Extracellular Signal-Regulated Kinase 1 and 2 Activation but Not CDK2 Activation or Cell Cycle Reentry. Mol. Cell. Biol. 23: 9303-9317 [Abstract] [Full Text]  
  • Fan, X., Liu, Y., Chen, J. J. (2003). Activation of c-Myc Contributes to Bovine Papillomavirus Type 1 E7-induced Cell Proliferation. J. Biol. Chem. 278: 43163-43168 [Abstract] [Full Text]  
  • Foster, J. S., Fernando, R. I., Ishida, N., Nakayama, K. I., Wimalasena, J. (2003). Estrogens Down-regulate p27Kip1 in Breast Cancer Cells through Skp2 and through Nuclear Export Mediated by the ERK Pathway. J. Biol. Chem. 278: 41355-41366 [Abstract] [Full Text]  
  • Ducruet, A. P., Lazo, J. S. (2003). Regulation of Cdc25A Half-life in Interphase by Cyclin-dependent Kinase 2 Activity. J. Biol. Chem. 278: 31838-31842 [Abstract] [Full Text]  
  • Petrenko, O., Fingerle-Rowson, G., Peng, T., Mitchell, R. A., Metz, C. N. (2003). Macrophage Migration Inhibitory Factor Deficiency Is Associated with Altered Cell Growth and Reduced Susceptibility to Ras-mediated Transformation. J. Biol. Chem. 278: 11078-11085 [Abstract] [Full Text]  
  • Qu, Z., Weiss, J. N., MacLellan, W. R. (2003). Regulation of the mammalian cell cycle: a model of the G1-to-S transition. Am. J. Physiol. Cell Physiol. 284: C349-C364 [Abstract] [Full Text]  
  • Busk, P. K, Bartkova, J., Strom, C. C, Wulf-Andersen, L., Hinrichsen, R., Christoffersen, T. E.H, Latella, L., Bartek, J., Haunso, S., Sheikh, S. P (2002). Involvement of cyclin D activity in left ventricle hypertrophy in vivo and in vitro. Cardiovasc Res 56: 64-75 [Abstract] [Full Text]  
  • Porter, L. A., Dellinger, R. W., Tynan, J. A., Barnes, E. A., Kong, M., Lenormand, J.-L., Donoghue, D. J. (2002). Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2. JCB 157: 357-366 [Abstract] [Full Text]  
  • Walter, K. A., Hossain, M. A., Luddy, C., Goel, N., Reznik, T. E., Laterra, J. (2002). Scatter Factor/Hepatocyte Growth Factor Stimulation of Glioblastoma Cell Cycle Progression through G1 Is c-Myc Dependent and Independent of p27 Suppression, Cdk2 Activation, or E2F1-Dependent Transcription. Mol. Cell. Biol. 22: 2703-2715 [Abstract] [Full Text]  
  • Sears, R. C., Nevins, J. R. (2002). Signaling Networks That Link Cell Proliferation and Cell Fate. J. Biol. Chem. 277: 11617-11620 [Full Text]  
  • Geng, Y., Yu, Q., Whoriskey, W., Dick, F., Tsai, K. Y., Ford, H. L., Biswas, D. K., Pardee, A. B., Amati, B., Jacks, T., Richardson, A., Dyson, N., Sicinski, P. (2001). Expression of cyclins E1 and E2 during mouse development and in neoplasia. Proc. Natl. Acad. Sci. USA 10.1073/pnas.231487798v1 [Abstract] [Full Text]  
  • Shih, H. H., Xiu, M., Berasi, S. P., Sampson, E. M., Leiter, A., Paulson, K. E., Yee, A. S. (2001). HMG Box Transcriptional Repressor HBP1 Maintains a Proliferation Barrier in Differentiated Liver Tissue. Mol. Cell. Biol. 21: 5723-5732 [Abstract] [Full Text]  
  • Moon, J. J., Nelson, B. H. (2001). Phosphatidylinositol 3-Kinase Potentiates, but Does Not Trigger, T Cell Proliferation Mediated by the IL-2 Receptor. J. Immunol. 167: 2714-2723 [Abstract] [Full Text]  
  • Eischen, C. M., Woo, D., Roussel, M. F., Cleveland, J. L. (2001). Apoptosis Triggered by Myc-Induced Suppression of Bcl-XL or Bcl-2 Is Bypassed during Lymphomagenesis. Mol. Cell. Biol. 21: 5063-5070 [Abstract] [Full Text]  
  • Jensen, S. S., Madsen, M. W., Lukas, J., Binderup, L., Bartek, J. (2001). Inhibitory Effects of 1{alpha},25-Dihydroxyvitamin D3 on the G1-S Phase-Controlling Machinery. Mol. Endocrinol. 15: 1370-1380 [Abstract] [Full Text]  
  • Noya, F., Chien, W.-M., Broker, T. R., Chow, L. T. (2001). p21cip1 Degradation in Differentiated Keratinocytes Is Abrogated by Costabilization with Cyclin E Induced by Human Papillomavirus E7. J. Virol. 75: 6121-6134 [Abstract] [Full Text]  
  • Lukas, C., Bartkova, J., Latella, L., Falck, J., Mailand, N., Schroeder, T., Sehested, M., Lukas, J., Bartek, J. (2001). DNA Damage-activated Kinase Chk2 Is Independent of Proliferation or Differentiation Yet Correlates with Tissue Biology. Cancer Res. 61: 4990-4993 [Abstract] [Full Text]  
  • Bardeesy, N., Bastian, B. C., Hezel, A., Pinkel, D., DePinho, R. A., Chin, L. (2001). Dual Inactivation of RB and p53 Pathways in RAS-Induced Melanomas. Mol. Cell. Biol. 21: 2144-2153 [Abstract] [Full Text]  
  • Schneider, M. D., MacLellan, W. R. (2001). Cyclin-Dependent Kinase-2 in the Birth and Death of Cardiac Muscle Cells. Circ. Res. 88: 367-369 [Full Text]  
  • Foster, J. S., Henley, D. C., Bukovsky, A., Seth, P., Wimalasena, J. (2001). Multifaceted Regulation of Cell Cycle Progression by Estrogen: Regulation of Cdk Inhibitors and Cdc25A Independent of Cyclin D1-Cdk4 Function. Mol. Cell. Biol. 21: 794-810 [Abstract] [Full Text]  
  • Kenney, A. M., Rowitch, D. H. (2000). Sonic hedgehog Promotes G1 Cyclin Expression and Sustained Cell Cycle Progression in Mammalian Neuronal Precursors. Mol. Cell. Biol. 20: 9055-9067 [Abstract] [Full Text]  
  • Sørensen, C. S., Lukas, C., Kramer, E. R., Peters, J.-M., Bartek, J., Lukas, J. (2000). Nonperiodic Activity of the Human Anaphase-Promoting Complex-Cdh1 Ubiquitin Ligase Results in Continuous DNA Synthesis Uncoupled from Mitosis. Mol. Cell. Biol. 20: 7613-7623 [Abstract] [Full Text]  
  • Geng, Y., Yu, Q., Whoriskey, W., Dick, F., Tsai, K. Y., Ford, H. L., Biswas, D. K., Pardee, A. B., Amati, B., Jacks, T., Richardson, A., Dyson, N., Sicinski, P. (2001). Expression of cyclins E1 and E2 during mouse development and in neoplasia. Proc. Natl. Acad. Sci. USA 98: 13138-13143 [Abstract] [Full Text]  
  • Porter, L. A., Dellinger, R. W., Tynan, J. A., Barnes, E. A., Kong, M., Lenormand, J.-L., Donoghue, D. J. (2002). Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2. JCB 157: 357-366 [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»