Cancer Research SABCS Telomeres
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
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 Email this article to a friend
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Markey, M. P.
Right arrow Articles by Knudsen, E. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Markey, M. P.
Right arrow Articles by Knudsen, E. S.
[Cancer Research 62, 6587-6597, November 15, 2002]
© 2002 American Association for Cancer Research

Molecular Biology and Genetics

Unbiased Analysis of RB-mediated Transcriptional Repression Identifies Novel Targets and Distinctions from E2F Action1

Michael P. Markey, Steven P. Angus, Matthew W. Strobeck, Sarah L. Williams, Ranjaka W. Gunawardena, Bruce J. Aronow and Erik S. Knudsen2

Department of Cell Biology, University of Cincinnati, Cincinnati, Ohio 45267-0521 [M. P. M., S. P. A., M. W. S., S. L. W., R. W. G., E. S. K.], and Divisions of Developmental Biology and Pediatric Informatics, The Children’s Hospital Research Foundation, Cincinnati, Ohio 45229-3039 [B. J. A.]

The retinoblastoma tumor suppressor, RB, is thought to inhibit cell cycle progression through transcriptional repression. E2F-regulated genes have been viewed as presumptive targets of RB-mediated repression. However, we found that specific E2F targets were not regulated in a consistent manner by the action of a RB allele that is refractory to cyclin-dependent kinase/cyclin-mediated phosphorylation (PSM-RB) when compared with E2F2 overproduction. Therefore, we used Affymetrix GeneChips as an unbiased approach to identify RB targets. We found that expression of PSM-RB significantly attenuates >200 targets, the majority of which are involved in cell cycle control (DNA replication or G2-M), DNA repair, or transcription/chromatin structure. The observed repression was due to the action of RB and not merely a manifestation of altered cell cycle distribution. Additionally, the majority of RB repression targets were confirmed through the blockade of endogenous RB phosphorylation via p16ink4a overexpression. Thus, these results have utility in assigning RB pathway activation in more complex systems of cell cycle inhibition (e.g., mitogen withdrawal, senescence, or DNA damage checkpoint). As expected, a significant fraction of RB-repressed genes have promoters that are bound/regulated by E2F family members. However, targets were identified that are distinct from genes known to be stimulated by overexpression of specific E2F proteins. Moreover, the relative action of RB versus E2F2 overexpression on specific genes demonstrates that a simple opposition model does not explain the relative contribution of RB to gene regulation. Thus, this study provides the first unbiased description of RB-repressed genes, thereby delineating new aspects of RB-mediated transcriptional control and novel targets involved in diverse cellular processes.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
K. R. Stengel, C. Thangavel, D. A. Solomon, S. P. Angus, Y. Zheng, and E. S. Knudsen
Retinoblastoma/p107/p130 Pocket Proteins: PROTEIN DYNAMICS AND INTERACTIONS WITH TARGET GENE PROMOTERS
J. Biol. Chem., July 17, 2009; 284(29): 19265 - 19271.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. A. Zagorski, E. S. Knudsen, and M. F. Reed
Retinoblastoma Deficiency Increases Chemosensitivity in Lung Cancer
Cancer Res., September 1, 2007; 67(17): 8264 - 8273.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. Teissier, Y. Ben Khalifa, M. Mori, P. Pautier, C. Desaintes, and F. Thierry
A New E6/P63 Pathway, Together with a Strong E7/E2F Mitotic Pathway, Modulates the Transcriptome in Cervical Cancer Cells
J. Virol., September 1, 2007; 81(17): 9368 - 9376.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
Y. Yung, J. L. Walker, J. M. Roberts, and R. K. Assoian
A Skp2 autoinduction loop and restriction point control
J. Cell Biol., August 27, 2007; 178(5): 741 - 747.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. V. Srinivasan, C. N. Mayhew, S. Schwemberger, W. Zagorski, and E. S. Knudsen
RB Loss Promotes Aberrant Ploidy by Deregulating Levels and Activity of DNA Replication Factors
J. Biol. Chem., August 17, 2007; 282(33): 23867 - 23877.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Sharma, C. E.S. Comstock, E. S. Knudsen, K. H. Cao, J. K. Hess-Wilson, L. M. Morey, J. Barrera, and K. E. Knudsen
Retinoblastoma Tumor Suppressor Status Is a Critical Determinant of Therapeutic Response in Prostate Cancer Cells
Cancer Res., July 1, 2007; 67(13): 6192 - 6203.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
J. Villanueva, Y. Yung, J. L. Walker, and R. K. Assoian
ERK Activity and G1 Phase Progression: Identifying Dispensable Versus Essential Activities and Primary Versus Secondary Targets
Mol. Biol. Cell, April 1, 2007; 18(4): 1457 - 1463.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
D. Kothapalli, L. Zhao, E. A. Hawthorne, Y. Cheng, E. Lee, E. Pure, and R. K. Assoian
Hyaluronan and CD44 antagonize mitogen-dependent cyclin D1 expression in mesenchymal cells
J. Cell Biol., February 12, 2007; 176(4): 535 - 544.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Cayrol, C. Lacroix, C. Mathe, V. Ecochard, M. Ceribelli, E. Loreau, V. Lazar, P. Dessen, R. Mantovani, L. Aguilar, et al.
The THAP-zinc finger protein THAP1 regulates endothelial cell proliferation through modulation of pRB/E2F cell-cycle target genes
Blood, January 15, 2007; 109(2): 584 - 594.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M. F. Reed, W. A. Zagorski, J. A. Howington, J. T. Zilfou, and E. S. Knudsen
Inhibition of retinoblastoma tumor suppressor activity by RNA interference in lung cancer lines.
Ann. Thorac. Surg., July 1, 2006; 82(1): 249 - 253.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
E. S. Knudsen and K. E. Knudsen
Retinoblastoma tumor suppressor: where cancer meets the cell cycle.
Experimental Biology and Medicine, July 1, 2006; 231(7): 1271 - 1281.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
F.-Q. An, H. M. Folarin, N. Compitello, J. Roth, S. L. Gerson, K. R. McCrae, F. D. Fakhari, D. P. Dittmer, and R. Renne
Long-Term-Infected Telomerase-Immortalized Endothelial Cells: a Model for Kaposi's Sarcoma-Associated Herpesvirus Latency In Vitro and In Vivo.
J. Virol., May 1, 2006; 80(10): 4833 - 4846.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Chen, X. Huang, D. Halicka, S. Brodsky, A. Avram, J. Eskander, N. A. Bloomgarden, Z. Darzynkiewicz, and M. S. Goligorsky
Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53
Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1575 - H1586.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. J. Miller, F. Rangwala, J. Williams, P. Ackerman, S. Kong, A. G. Jegga, S. Kaiser, B. J. Aronow, S. Frahm, L. Kluwe, et al.
Large-scale molecular comparison of human schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues.
Cancer Res., March 1, 2006; 66(5): 2584 - 2591.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Melcon, S. Kozlov, D. A. Cutler, T. Sullivan, L. Hernandez, P. Zhao, S. Mitchell, G. Nader, M. Bakay, J. N. Rottman, et al.
Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration
Hum. Mol. Genet., February 15, 2006; 15(4): 637 - 651.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
P.-L. Chen, F. Liu, S. Cai, X. Lin, A. Li, Y. Chen, B. Gu, E. Y.-H. P. Lee, and W.-H. Lee
Inactivation of CtIP Leads to Early Embryonic Lethality Mediated by G1 Restraint and to Tumorigenesis by Haploid Insufficiency
Mol. Cell. Biol., May 1, 2005; 25(9): 3535 - 3542.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. T. McCabe, J. N. Davis, and M. L. Day
Regulation of DNA Methyltransferase 1 by the pRb/E2F1 Pathway
Cancer Res., May 1, 2005; 65(9): 3624 - 3632.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. W. Jackson, M. K. Agarwal, J. Yang, P. Bruss, T. Uchiumi, M. L. Agarwal, G. R. Stark, and W. R. Taylor,
p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2
J. Cell Sci., May 1, 2005; 118(9): 1821 - 1832.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
E. E. Bosco and E. S. Knudsen
Differential role of RB in response to UV and IR damage
Nucleic Acids Res., March 14, 2005; 33(5): 1581 - 1592.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F.-Q. An, N. Compitello, E. Horwitz, M. Sramkoski, E. S. Knudsen, and R. Renne
The Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus Modulates Cellular Gene Expression and Protects Lymphoid Cells from p16 INK4A-induced Cell Cycle Arrest
J. Biol. Chem., February 4, 2005; 280(5): 3862 - 3874.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. W. Fry, P. J. Harvey, P. R. Keller, W. L. Elliott, M. Meade, E. Trachet, M. Albassam, X. Zheng, W. R. Leopold, N. K. Pryer, et al.
Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts
Mol. Cancer Ther., November 1, 2004; 3(11): 1427 - 1438.
[Abstract] [Full Text] [PDF]

Home page
 Plant CellHome page
O. A. Koroleva, M. Tomlinson, P. Parinyapong, L. Sakvarelidze, D. Leader, P. Shaw, and J. H. Doonan
CycD1, a Putative G1 Cyclin from Antirrhinum majus, Accelerates the Cell Cycle in Cultured Tobacco BY-2 Cells by Enhancing Both G1/S Entry and Progression through S and G2 Phases
PLANT CELL, September 1, 2004; 16(9): 2364 - 2379.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Markey, H. Siddiqui, and E. S. Knudsen
Geminin Is Targeted for Repression by the Retinoblastoma Tumor Suppressor Pathway through Intragenic E2F Sites
J. Biol. Chem., July 9, 2004; 279(28): 29255 - 29262.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. W. Gunawardena, H. Siddiqui, D. A. Solomon, C. N. Mayhew, J. Held, S. P. Angus, and E. S. Knudsen
Hierarchical Requirement of SWI/SNF in Retinoblastoma Tumor Suppressor-mediated Repression of Plk1
J. Biol. Chem., July 9, 2004; 279(28): 29278 - 29285.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. P. Angus, C. N. Mayhew, D. A. Solomon, W. A. Braden, M. P. Markey, Y. Okuno, M. C. Cardoso, D. M. Gilbert, and E. S. Knudsen
RB Reversibly Inhibits DNA Replication via Two Temporally Distinct Mechanisms
Mol. Cell. Biol., June 15, 2004; 24(12): 5404 - 5420.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Thierry, M. A. Benotmane, C. Demeret, M. Mori, S. Teissier, and C. Desaintes
A Genomic Approach Reveals a Novel Mitotic Pathway in Papillomavirus Carcinogenesis
Cancer Res., February 1, 2004; 64(3): 895 - 903.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
E. E. Bosco, C. N. Mayhew, R. F. Hennigan, J. Sage, T. Jacks, and E. S. Knudsen
RB signaling prevents replication-dependent DNA double-strand breaks following genotoxic insult
Nucleic Acids Res., January 2, 2004; 32(1): 25 - 34.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Vernell, K. Helin, and H. Muller
Identification of Target Genes of the p16INK4A-pRB-E2F Pathway
J. Biol. Chem., November 14, 2003; 278(46): 46124 - 46137.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H. Siddiqui, D. A. Solomon, R. W. Gunawardena, Y. Wang, and E. S. Knudsen
Histone Deacetylation of RB-Responsive Promoters: Requisite for Specific Gene Repression but Dispensable for Cell Cycle Inhibition
Mol. Cell. Biol., November 1, 2003; 23(21): 7719 - 7731.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Lohr, C. Moritz, A. Contente, and M. Dobbelstein
p21/CDKN1A Mediates Negative Regulation of Transcription by p53
J. Biol. Chem., August 29, 2003; 278(35): 32507 - 32516.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
D. S. Fay, E. Large, M. Han, and M. Darland
lin-35/Rb and ubc-18, an E2 ubiquitin-conjugating enzyme, function redundantly to control pharyngeal morphogenesis in C. elegans
Development, July 15, 2003; 130(14): 3319 - 3330.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2002 by the American Association for Cancer Research.