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 Wang, S.
Right arrow Articles by Chellappan, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, S.
Right arrow Articles by Chellappan, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 1999, p. 7447-7460, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Rb and Prohibitin Target Distinct Regions of E2F1 for Repression and Respond to Different Upstream Signals

Sheng Wang, Niharika Nath, Gina Fusaro, and Srikumar Chellappan*

Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Received 19 January 1999/Returned for modification 22 March 1999/Accepted 2 August 1999

E2F transcription factor is subject to stringent regulation by a variety of molecules. We recently observed that prohibitin, a potential tumor suppressor protein, binds to the retinoblastoma (Rb) protein and represses E2F transcriptional activity. Here we demonstrate that prohibitin requires the marked box region of E2F for repression; further, prohibitin can effectively inhibit colony formation induced by overexpression of E2F1 in T47D cells. Prohibitin was also found to interact with the signaling kinase c-Raf-1, and Raf-1 could effectively reverse prohibitin-mediated repression of E2F activity. Agents such as E1A, p38 kinase, and cyclins D and E had no effect on prohibitin-mediated repression of E2F1, but all of these molecules could reverse Rb function. Similarly, stimulation of the immunoglobulin M signaling pathway in Ramos cells could inactivate prohibitin, but this had no effect on Rb function. Serum stimulation of quiescent Ramos cells inactivated Rb and prohibitin with different kinetics; further, while the serum-dependent inactivation of Rb was dependent on cyclin-dependent kinase activity, the inactivation of prohibitin was not. We believe that prohibitin is a novel regulator of E2F function which channels specific signaling cascades to the cell cycle regulatory machinery.

* Corresponding author. Mailing address: Department of Pathology, College of Physicians and Surgeons, Columbia University, 630W 168th St., New York, NY 10032. Phone: (212) 305-3736. Fax: (212) 305-5498. E-mail: spc10{at}columbia.edu.

Molecular and Cellular Biology, November 1999, p. 7447-7460, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Dai, Y., Ngo, D., Jacob, J., Forman, L. W., Faller, D. V. (2008). Prohibitin and the SWI/SNF ATPase subunit BRG1 are required for effective androgen antagonist-mediated transcriptional repression of androgen receptor-regulated genes. Carcinogenesis 29: 1725-1733 [Abstract] [Full Text]  
  • Ross, J. A., Nagy, Z. S., Kirken, R. A. (2008). The PHB1/2 Phosphocomplex Is Required for Mitochondrial Homeostasis and Survival of Human T Cells. J. Biol. Chem. 283: 4699-4713 [Abstract] [Full Text]  
  • He, B., Feng, Q., Mukherjee, A., Lonard, D. M., DeMayo, F. J., Katzenellenbogen, B. S., Lydon, J. P., O'Malley, B. W. (2008). A Repressive Role for Prohibitin in Estrogen Signaling. Mol. Endocrinol. 22: 344-360 [Abstract] [Full Text]  
  • Chowdhury, I., Xu, W., Stiles, J. K., Zeleznik, A., Yao, X., Matthews, R., Thomas, K., Thompson, W. E. (2007). Apoptosis of Rat Granulosa Cells after Staurosporine and Serum Withdrawal Is Suppressed by Adenovirus-Directed Overexpression of Prohibitin. Endocrinology 148: 206-217 [Abstract] [Full Text]  
  • Hayashi, R., Goto, Y., Ikeda, R., Yokoyama, K. K., Yoshida, K. (2006). CDCA4 Is an E2F Transcription Factor Family-induced Nuclear Factor That Regulates E2F-dependent Transcriptional Activation and Cell Proliferation. J. Biol. Chem. 281: 35633-35648 [Abstract] [Full Text]  
  • Kasashima, K., Ohta, E., Kagawa, Y., Endo, H. (2006). Mitochondrial Functions and Estrogen Receptor-dependent Nuclear Translocation of Pleiotropic Human Prohibitin 2. J. Biol. Chem. 281: 36401-36410 [Abstract] [Full Text]  
  • Peng, X., Mehta, R., Wang, S., Chellappan, S., Mehta, R. G. (2006). Prohibitin is a novel target gene of vitamin d involved in its antiproliferative action in breast cancer cells.. Cancer Res. 66: 7361-7369 [Abstract] [Full Text]  
  • Rastogi, S., Joshi, B., Dasgupta, P., Morris, M., Wright, K., Chellappan, S. (2006). Prohibitin Facilitates Cellular Senescence by Recruiting Specific Corepressors To Inhibit E2F Target Genes.. Mol. Cell. Biol. 26: 4161-4171 [Abstract] [Full Text]  
  • He, F., Fenner, B. J., Godwin, A. K., Kwang, J. (2006). White Spot Syndrome Virus Open Reading Frame 222 Encodes a Viral E3 Ligase and Mediates Degradation of a Host Tumor Suppressor via Ubiquitination.. J. Virol. 80: 3884-3892 [Abstract] [Full Text]  
  • Rastogi, S., Joshi, B., Fusaro, G., Chellappan, S. (2006). Camptothecin Induces Nuclear Export of Prohibitin Preferentially in Transformed Cells through a CRM-1-dependent Mechanism. J. Biol. Chem. 281: 2951-2959 [Abstract] [Full Text]  
  • Liu, D. X., Nath, N., Chellappan, S. P., Greene, L. A. (2005). Regulation of neuron survival and death by p130 and associated chromatin modifiers. Genes Dev. 19: 719-732 [Abstract] [Full Text]  
  • Sharma, A., Qadri, A. (2004). Vi polysaccharide of Salmonella typhi targets the prohibitin family of molecules in intestinal epithelial cells and suppresses early inflammatory responses. Proc. Natl. Acad. Sci. USA 101: 17492-17497 [Abstract] [Full Text]  
  • Thompson, W. E., Asselin, E., Branch, A., Stiles, J. K., Sutovsky, P., Lai, L., Im, G.-S., Prather, R. S., Isom, S. C., Rucker, E. III, Tsang, B. K. (2004). Regulation of Prohibitin Expression During Follicular Development and Atresia in the Mammalian Ovary. Biol. Reprod. 71: 282-290 [Abstract] [Full Text]  
  • Sun, L., Liu, L., Yang, X.-J., Wu, Z. (2004). Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation. J. Cell Sci. 117: 3021-3029 [Abstract] [Full Text]  
  • Frolov, M. V., Dyson, N. J. (2004). Molecular mechanisms of E2F-dependent activation and pRB-mediated repression. J. Cell Sci. 117: 2173-2181 [Abstract] [Full Text]  
  • Liu, K., Luo, Y., Lin, F.-T., Lin, W.-C. (2004). TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival. Genes Dev. 18: 673-686 [Abstract] [Full Text]  
  • Fusaro, G., Dasgupta, P., Rastogi, S., Joshi, B., Chellappan, S. (2003). Prohibitin Induces the Transcriptional Activity of p53 and Is Exported from the Nucleus upon Apoptotic Signaling. J. Biol. Chem. 278: 47853-47861 [Abstract] [Full Text]  
  • Manjeshwar, S., Branam, D. E., Lerner, M. R., Brackett, D. J., Jupe, E. R. (2003). Tumor Suppression by the Prohibitin Gene 3'Untranslated Region RNA in Human Breast Cancer. Cancer Res. 63: 5251-5256 [Abstract] [Full Text]  
  • Sanz, M. A., Tsang, W. Y., Willems, E. M., Grivell, L. A., Lemire, B. D., van der Spek, H., Nijtmans, L. G. J. (2003). The Mitochondrial Prohibitin Complex Is Essential for Embryonic Viability and Germline Function in Caenorhabditis elegans. J. Biol. Chem. 278: 32091-32099 [Abstract] [Full Text]  
  • Thompson, W. E., Branch, A., Whittaker, J. A., Lyn, D., Zilberstein, M., Mayo, K. E., Thomas, K. (2001). Characterization of Prohibitin in a Newly Established Rat Ovarian Granulosa Cell Line. Endocrinology 142: 4076-4085 [Abstract] [Full Text]  
  • Xia, C., Bao, Z., Tabassam, F., Ma, W., Qiu, M., Hua, S.-b., Liu, M. (2000). GCIP, a Novel Human Grap2 and Cyclin D Interacting Protein, Regulates E2F-mediated Transcriptional Activity. J. Biol. Chem. 275: 20942-20948 [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»