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 Sterner, J. M.
Right arrow Articles by Horowitz, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sterner, J. M.
Right arrow Articles by Horowitz, J. M.

 Previous Article  |  Next Article 

Mol Cell Biol, May 1998, p. 2748-2757, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Negative Regulation of DNA Replication by the Retinoblastoma Protein Is Mediated by Its Association with MCM7

Jacqueline M. Sterner,1,2 Susan Dew-Knight,1,2 Christine Musahl,3 Sally Kornbluth,1,4 and Jonathan M. Horowitz1,2,*

Departments of Molecular Cancer Biology,1 Microbiology,2 and Cell Biology,4 Duke University Medical Center, Durham, North Carolina 27710, and the Division of Biology, Universitat Konstanz, D 77434 Konstanz, Federal Republic of Germany3

Received 29 October 1997/Returned for modification 4 December 1997/Accepted 13 February 1998

A yeast two-hybrid screen was employed to identify human proteins that specifically bind the amino-terminal 400 amino acids of the retinoblastoma (Rb) protein. Two independent cDNAs resulting from this screen were found to encode the carboxy-terminal 137 amino acids of MCM7, a member of a family of proteins that comprise replication licensing factor. Full-length Rb and MCM7 form protein complexes in vitro, and the amino termini of two Rb-related proteins, p107 and p130, also bind MCM7. Protein complexes between Rb and MCM7 were also detected in anti-Rb immunoprecipitates prepared from human cells. The amino-termini of Rb and p130 strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopus in vitro DNA replication assay system. These data provide the first evidence that Rb and Rb-related proteins can directly regulate DNA replication and that components of licensing factor are targets of the products of tumor suppressor genes.

* Corresponding author. Present address: Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine North Carolina State University, Raleigh, NC 27606. Phone: (919) 515 4479. Fax: (919) 515 3044. E-mail: jon_horowitz{at}ncsu.edu.

Mol Cell Biol, May 1998, p. 2748-2757, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ferguson, R. L., Maller, J. L. (2008). Cyclin E-dependent localization of MCM5 regulates centrosome duplication. J. Cell Sci. 121: 3224-3232 [Abstract] [Full Text]  
  • Bochman, M. L., Bell, S. P., Schwacha, A. (2008). Subunit Organization of Mcm2-7 and the Unequal Role of Active Sites in ATP Hydrolysis and Viability. Mol. Cell. Biol. 28: 5865-5873 [Abstract] [Full Text]  
  • Liu, E., Lee, A. Y.-L., Chiba, T., Olson, E., Sun, P., Wu, X. (2007). The ATR-mediated S phase checkpoint prevents rereplication in mammalian cells when licensing control is disrupted. JCB 179: 643-657 [Abstract] [Full Text]  
  • Braden, W. A., Lenihan, J. M., Lan, Z., Luce, K. S., Zagorski, W., Bosco, E., Reed, M. F., Cook, J. G., Knudsen, E. S. (2006). Distinct Action of the Retinoblastoma Pathway on the DNA Replication Machinery Defines Specific Roles for Cyclin-Dependent Kinase Complexes in Prereplication Complex Assembly and S-Phase Progression. Mol. Cell. Biol. 26: 7667-7681 [Abstract] [Full Text]  
  • Liu, P., Barkley, L. R., Day, T., Bi, X., Slater, D. M., Alexandrow, M. G., Nasheuer, H.-P., Vaziri, C. (2006). The Chk1-mediated S-phase Checkpoint Targets Initiation Factor Cdc45 via a Cdc25A/Cdk2-independent Mechanism. J. Biol. Chem. 281: 30631-30644 [Abstract] [Full Text]  
  • Knudsen, E. S., Knudsen, K. E. (2006). Retinoblastoma tumor suppressor: where cancer meets the cell cycle.. Exp. Biol. Med. 231: 1271-1281 [Abstract] [Full Text]  
  • Baltin, J., Leist, S., Odronitz, F., Wollscheid, H.-P., Baack, M., Kapitza, T., Schaarschmidt, D., Knippers, R. (2006). DNA Replication in Protein Extracts from Human Cells Requires ORC and Mcm Proteins. J. Biol. Chem. 281: 12428-12435 [Abstract] [Full Text]  
  • Liu, F., Lee, W.-H. (2006). CtIP Activates Its Own and Cyclin D1 Promoters via the E2F/RB Pathway during G1/S Progression. Mol. Cell. Biol. 26: 3124-3134 [Abstract] [Full Text]  
  • Snyder, M., He, W., Zhang, J. J. (2005). The DNA replication factor MCM5 is essential for Stat1-mediated transcriptional activation. Proc. Natl. Acad. Sci. USA 102: 14539-14544 [Abstract] [Full Text]  
  • Chen, P.-L., Liu, F., Cai, S., Lin, X., Li, A., Chen, Y., Gu, B., Lee, E. Y.-H. P., Lee, W.-H. (2005). Inactivation of CtIP Leads to Early Embryonic Lethality Mediated by G1 Restraint and to Tumorigenesis by Haploid Insufficiency. Mol. Cell. Biol. 25: 3535-3542 [Abstract] [Full Text]  
  • Cortez, D. (2005). Unwind and slow down: checkpoint activation by helicase and polymerase uncoupling. Genes Dev. 19: 1007-1012 [Full Text]  
  • Byun, T. S., Pacek, M., Yee, M.-c., Walter, J. C., Cimprich, K. A. (2005). Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev. 19: 1040-1052 [Abstract] [Full Text]  
  • Bosco, E. E., Knudsen, E. S. (2005). Differential role of RB in response to UV and IR damage. Nucleic Acids Res 33: 1581-1592 [Abstract] [Full Text]  
  • Naderi, S., Wang, J. Y.J., Chen, T.-T., Gutzkow, K. B., Blomhoff, H. K. (2005). cAMP-mediated Inhibition of DNA Replication and S Phase Progression: Involvement of Rb, p21Cip1, and PCNA. Mol. Biol. Cell 16: 1527-1542 [Abstract] [Full Text]  
  • Ha, S.-A., Shin, S. M., Namkoong, H., Lee, H., Cho, G. W., Hur, S. Y., Kim, T. E., Kim, J. W. (2004). Cancer-Associated Expression of Minichromosome Maintenance 3 Gene in Several Human Cancers and Its Involvement in Tumorigenesis. Clin. Cancer Res. 10: 8386-8395 [Abstract] [Full Text]  
  • Kinoshita, Y., Johnson, E. M. (2004). Site-specific Loading of an MCM Protein Complex in a DNA Replication Initiation Zone Upstream of the c-MYC Gene in the HeLa Cell Cycle. J. Biol. Chem. 279: 35879-35889 [Abstract] [Full Text]  
  • Shechter, D., Gautier, J. (2004). MCM proteins and checkpoint kinases get together at the fork. Proc. Natl. Acad. Sci. USA 101: 10845-10846 [Full Text]  
  • Cortez, D., Glick, G., Elledge, S. J. (2004). From The Cover: Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc. Natl. Acad. Sci. USA 101: 10078-10083 [Abstract] [Full Text]  
  • Yin, M.-B., Li, Z.-R., Cao, S., Durrani, F. A., Azrak, R. G., Frank, C., Rustum, Y. M. (2004). Enhanced 7-Ethyl-10-hydroxycamptothecin (SN-38) Lethality by Methylselenocysteine Is Associated with Chk2 Phosphorylation at Threonine-68 and Down-Regulation of Cdc6 Expression. Mol. Pharmacol. 66: 153-160 [Abstract] [Full Text]  
  • Angus, S. P., Mayhew, C. N., Solomon, D. A., Braden, W. A., Markey, M. P., Okuno, Y., Cardoso, M. C., Gilbert, D. M., Knudsen, E. S. (2004). RB Reversibly Inhibits DNA Replication via Two Temporally Distinct Mechanisms. Mol. Cell. Biol. 24: 5404-5420 [Abstract] [Full Text]  
  • Forsburg, S. L. (2004). Eukaryotic MCM Proteins: Beyond Replication Initiation. Microbiol. Mol. Biol. Rev. 68: 109-131 [Abstract] [Full Text]  
  • Roig, J. M., Molina, M. A., Cascante, A., Calbo, J., Carbo, N., Wirtz, U., Sreedharan, S., Fillat, C., Mazo, A. (2004). Adenovirus-Mediated Retinoblastoma 94 Gene Transfer Induces Human Pancreatic Tumor Regression in a Mouse Xenograft Model. Clin. Cancer Res. 10: 1454-1462 [Abstract] [Full Text]  
  • Harvey, K. J., Newport, J. (2003). CpG Methylation of DNA Restricts Prereplication Complex Assembly in Xenopus Egg Extracts. Mol. Cell. Biol. 23: 6769-6779 [Abstract] [Full Text]  
  • Owen, A. B., Stuart, J., Mach, K., Villeneuve, A. M., Kim, S. (2003). A Gene Recommender Algorithm to Identify Coexpressed Genes in C. elegans. Genome Res 13: 1828-1837 [Abstract] [Full Text]  
  • Dziak, R., Leishman, D., Radovic, M., Tye, B. K., Yankulov, K. (2003). Evidence for a Role of MCM (Mini-chromosome Maintenance)5 in Transcriptional Repression of Sub-telomeric and Ty-proximal Genes in Saccharomyces cerevisiae. J. Biol. Chem. 278: 27372-27381 [Abstract] [Full Text]  
  • Fitch, M. J., Donato, J. J., Tye, B. K. (2003). Mcm7, a Subunit of the Presumptive MCM Helicase, Modulates Its Own Expression in Conjunction with Mcm1. J. Biol. Chem. 278: 25408-25416 [Abstract] [Full Text]  
  • Xin, S., Weng, L., Xu, J., Du, W. (2003). The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth. Development 129: 1345-1356 [Abstract] [Full Text]  
  • Dimitrova, D. S., Berezney, R. (2002). The spatio-temporal organization of DNA replication sites is identical in primary, immortalized and transformed mammalian cells. J. Cell Sci. 115: 4037-4051 [Abstract] [Full Text]  
  • Xie, A.-Y., Folk, W. R. (2002). Inhibition of Polyomavirus ori-Dependent DNA Replication by mSin3B. J. Virol. 76: 11809-11818 [Abstract] [Full Text]  
  • Schaarschmidt, D., Ladenburger, E.-M., Keller, C., Knippers, R. (2002). Human Mcm proteins at a replication origin during the G1 to S phase transition. Nucleic Acids Res 30: 4176-4185 [Abstract] [Full Text]  
  • Yang, H., Williams, B. O., Hinds, P. W., Shih, T. S., Jacks, T., Bronson, R. T., Livingston, D. M. (2002). Tumor Suppression by a Severely Truncated Species of Retinoblastoma Protein. Mol. Cell. Biol. 22: 3103-3110 [Abstract] [Full Text]  
  • Lefevre, S H, Chauveinc, L, Stoppa-Lyonnet, D, Michon, J, Lumbroso, L, Berthet, P, Frappaz, D, Dutrillaux, B, Chevillard, S, Malfoy, B (2002). A T to C mutation in the polypyrimidine tract of the exon 9 splicing site of the RB1 gene responsible for low penetrance hereditary retinoblastoma. J. Med. Genet. 39: e21-21 [Full Text]  
  • Kennett, S. B., Moorefield, K. S., Horowitz, J. M. (2002). Sp3 Represses Gene Expression via the Titration of Promoter-specific Transcription Factors. J. Biol. Chem. 277: 9780-9789 [Abstract] [Full Text]  
  • Shohet, J. M., Hicks, M. J., Plon, S. E., Burlingame, S. M., Stuart, S., Chen, S.-Y., Brenner, M. K., Nuchtern, J. G. (2002). Minichromosome Maintenance Protein MCM7 Is a Direct Target of the MYCN Transcription Factor in Neuroblastoma. Cancer Res. 62: 1123-1128 [Abstract] [Full Text]  
  • Harbour, J. W. (2001). Molecular Basis of Low-Penetrance Retinoblastoma. Arch Ophthalmol 119: 1699-1704 [Abstract] [Full Text]  
  • DaFonseca, C. J., Shu, F., Zhang, J. J. (2001). Identification of two residues in MCM5 critical for the assembly of minichromosome maintenance complexes and signal transducer and activator of transcription-mediated transcription activation in response to IFN-gamma. Proc. Natl. Acad. Sci. USA 10.1073/pnas.061487598v1 [Abstract] [Full Text]  
  • Harbour, J. W., Dean, D. C. (2000). The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 14: 2393-2409 [Full Text]  
  • Chien, W.-M., Parker, J. N., Schmidt-Grimminger, D.-C., Broker, T. R., Chow, L. T. (2000). Casein Kinase II Phosphorylation of the Human Papillomavirus-18 E7 Protein Is Critical for Promoting S-Phase Entry. Cell Growth Differ. 11: 425-435 [Abstract] [Full Text]  
  • Mal, A., Chattopadhyay, D., Ghosh, M. K., Poon, R. Y.C., Hunter, T., Harter, M. L. (2000). P21 and Retinoblastoma Protein Control the Absence of DNA Replication in Terminally Differentiated Muscle Cells. JCB 149: 281-292 [Abstract] [Full Text]  
  • Springer, P., Holding, D., Groover, A, Yordan, C, Martienssen, R. (2000). The essential Mcm7 protein PROLIFERA is localized to the nucleus of dividing cells during the G(1) phase and is required maternally for early Arabidopsis development. Development 127: 1815-1822 [Abstract]  
  • Doostzadeh-Cizeron, J., Evans, R., Yin, S., Goodrich, D. W. (1999). Apoptosis Induced by the Nuclear Death Domain Protein p84N5 Is Inhibited by Association with Rb Protein. Mol. Biol. Cell 10: 3251-3261 [Abstract] [Full Text]  
  • Driscoll, B., T'Ang, A., Hu, Y.-H., Yan, C. L., Fu, Y., Luo, Y., Wu, K. J., Wen, S., Shi, X.-H., Barsky, L., Weinberg, K., Murphree, A. L., Fung, Y. K. (1999). Discovery of a Regulatory Motif That Controls the Exposure of Specific Upstream Cyclin-dependent Kinase Sites That Determine Both Conformation and Growth Suppressing Activity of pRb. J. Biol. Chem. 274: 9463-9471 [Abstract] [Full Text]  
  • Reynisdóttir, I., Bhattacharyya, S., Zhang, D., Prives, C. (1999). The Retinoblastoma Protein Alters the Phosphorylation State of Polyomavirus Large T Antigen in Murine Cell Extracts and Inhibits Polyomavirus Origin DNA Replication. J. Virol. 73: 3004-3013 [Abstract] [Full Text]  
  • Kuhne, C., Banks, L. (1998). E3-Ubiquitin Ligase/E6-AP Links Multicopy Maintenance Protein 7 to the Ubiquitination Pathway by a Novel Motif, the L2G Box. J. Biol. Chem. 273: 34302-34309 [Abstract] [Full Text]  
  • Kondo, T., Higashi, H., Nishizawa, H., Ishikawa, S., Ashizawa, S., Yamada, M., Makita, Z., Koike, T., Hatakeyama, M. (2001). Involvement of pRB-related p107 Protein in the Inhibition of S Phase Progression in Response to Genotoxic Stress. J. Biol. Chem. 276: 17559-17567 [Abstract] [Full Text]  
  • Alexandrow, M. G., Ritzi, M., Pemov, A., Hamlin, J. L. (2002). A Potential Role for Mini-chromosome Maintenance (MCM) Proteins in Initiation at the Dihydrofolate Reductase Replication Origin. J. Biol. Chem. 277: 2702-2708 [Abstract] [Full Text]  
  • DaFonseca, C. J., Shu, F., Zhang, J. J. (2001). Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-gamma. Proc. Natl. Acad. Sci. USA 98: 3034-3039 [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»