MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 1999 by the American Society for Microbiology. All rights reserved.