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 Dey, A.
Right arrow Articles by Ozato, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dey, A.
Right arrow Articles by Ozato, K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2000, p. 6537-6549, Vol. 20, No. 17
0270-7306/00/$04.00+0

A Bromodomain Protein, MCAP, Associates with Mitotic Chromosomes and Affects G2-to-M Transition

Anup Dey,1 Jan Ellenberg,2,dagger Andrea Farina,1 Allen E. Coleman,3 Tetsuo Maruyama,1,Dagger Selvaggia Sciortino,1 Jennifer Lippincott-Schwartz,2 and Keiko Ozato1,*

Laboratory of Molecular Growth Regulation,1 and Cell Biology and Metabolism Branch,2 National Institute of Child Health and Human Development, and Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute,3 National Institutes of Health, Bethesda, Maryland 20892-2753

Received 22 November 1999/Returned for modification 2 February 2000/Accepted 2 June 2000

We describe a novel nuclear factor called mitotic chromosome-associated protein (MCAP), which belongs to the poorly understood BET subgroup of the bromodomain superfamily. Expression of the 200-kDa MCAP was linked to cell division, as it was induced by growth stimulation and repressed by growth inhibition. The most notable feature of MCAP was its association with chromosomes during mitosis, observed at a time when the majority of nuclear regulatory factors were released into the cytoplasm, coinciding with global cessation of transcription. Indicative of its predominant interaction with euchromatin, MCAP localized on mitotic chromosomes with exquisite specificity: (i) MCAP-chromosome association became evident subsequent to the initiation of histone H3 phosphorylation and early chromosomal condensation; and (ii) MCAP was absent from centromeres, the sites of heterochromatin. Supporting a role for MCAP in G2/M transition, microinjection of anti-MCAP antibody into HeLa cell nuclei completely inhibited the entry into mitosis, without abrogating the ongoing DNA replication. These results suggest that MCAP plays a role in a process governing chromosomal dynamics during mitosis.

* Corresponding author. Mailing address: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development. Bldg. 6, Rm. 2A01, National Institutes of Health, Bethesda, MD 20892-2753. Phone: (301) 496-9184. Fax: (301) 480-9354. E-mail: ozatok{at}nih.gov.

dagger Present address: Gene Expression and Cell Biology/Biophysics Programmes, European Molecular Biology Laboratory, Heidelberg, Germany.

Dagger Present address: Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.

Molecular and Cellular Biology, September 2000, p. 6537-6549, Vol. 20, No. 17
0270-7306/00/$04.00+0


This article has been cited by other articles:

  • Ottinger, M., Pliquet, D., Christalla, T., Frank, R., Stewart, J. P., Schulz, T. F. (2009). The Interaction of the Gammaherpesvirus 68 orf73 Protein with Cellular BET Proteins Affects the Activation of Cell Cycle Promoters. J. Virol. 83: 4423-4434 [Abstract] [Full Text]  
  • Jang, M. K., Kwon, D., McBride, A. A. (2009). Papillomavirus E2 Proteins and the Host Brd4 Protein Associate with Transcriptionally Active Cellular Chromatin. J. Virol. 83: 2592-2600 [Abstract] [Full Text]  
  • Poddar, A., Reed, S. C., McPhillips, M. G., Spindler, J. E., McBride, A. A. (2009). The Human Papillomavirus Type 8 E2 Tethering Protein Targets the Ribosomal DNA Loci of Host Mitotic Chromosomes. J. Virol. 83: 640-650 [Abstract] [Full Text]  
  • Zhou, M., Huang, K., Jung, K.-J., Cho, W.-K., Klase, Z., Kashanchi, F., Pise-Masison, C. A., Brady, J. N. (2009). Bromodomain Protein Brd4 Regulates Human Immunodeficiency Virus Transcription through Phosphorylation of CDK9 at Threonine 29. J. Virol. 83: 1036-1044 [Abstract] [Full Text]  
  • Lin, A., Wang, S., Nguyen, T., Shire, K., Frappier, L. (2008). The EBNA1 Protein of Epstein-Barr Virus Functionally Interacts with Brd4. J. Virol. 82: 12009-12019 [Abstract] [Full Text]  
  • Cardenas-Mora, J., Spindler, J. E., Jang, M. K., McBride, A. A. (2008). Dimerization of the Papillomavirus E2 Protein Is Required for Efficient Mitotic Chromosome Association and Brd4 Binding. J. Virol. 82: 7298-7305 [Abstract] [Full Text]  
  • Crawford, N. P. S., Alsarraj, J., Lukes, L., Walker, R. C., Officewala, J. S., Yang, H. H., Lee, M. P., Ozato, K., Hunter, K. W. (2008). Bromodomain 4 activation predicts breast cancer survival. Proc. Natl. Acad. Sci. USA 105: 6380-6385 [Abstract] [Full Text]  
  • Mochizuki, K., Nishiyama, A., Jang, M. K., Dey, A., Ghosh, A., Tamura, T., Natsume, H., Yao, H., Ozato, K. (2008). The Bromodomain Protein Brd4 Stimulates G1 Gene Transcription and Promotes Progression to S Phase. J. Biol. Chem. 283: 9040-9048 [Abstract] [Full Text]  
  • Yang, Z., He, N., Zhou, Q. (2008). Brd4 Recruits P-TEFb to Chromosomes at Late Mitosis To Promote G1 Gene Expression and Cell Cycle Progression. Mol. Cell. Biol. 28: 967-976 [Abstract] [Full Text]  
  • Schweiger, M.-R., Ottinger, M., You, J., Howley, P. M. (2007). Brd4-Independent Transcriptional Repression Function of the Papillomavirus E2 Proteins. J. Virol. 81: 9612-9622 [Abstract] [Full Text]  
  • Wu, S.-Y., Chiang, C.-M. (2007). The Double Bromodomain-containing Chromatin Adaptor Brd4 and Transcriptional Regulation. J. Biol. Chem. 282: 13141-13145 [Abstract] [Full Text]  
  • Nagashima, T., Maruyama, T., Furuya, M., Kajitani, T., Uchida, H., Masuda, H., Ono, M., Arase, T., Ozato, K., Yoshimura, Y. (2007). Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis. Mol Hum Reprod 13: 141-148* [Abstract] [Full Text]  
  • Lenburg, M. E., Sinha, A., Faller, D. V., Denis, G. V. (2007). Tumor-specific and Proliferation-specific Gene Expression Typifies Murine Transgenic B Cell Lymphomagenesis. J. Biol. Chem. 282: 4803-4811 [Abstract] [Full Text]  
  • Nakamura, Y., Umehara, T., Nakano, K., Jang, M. K., Shirouzu, M., Morita, S., Uda-Tochio, H., Hamana, H., Terada, T., Adachi, N., Matsumoto, T., Tanaka, A., Horikoshi, M., Ozato, K., Padmanabhan, B., Yokoyama, S. (2007). Crystal Structure of the Human BRD2 Bromodomain: INSIGHTS INTO DIMERIZATION AND RECOGNITION OF ACETYLATED HISTONE H4. J. Biol. Chem. 282: 4193-4201 [Abstract] [Full Text]  
  • Ottinger, M., Christalla, T., Nathan, K., Brinkmann, M. M., Viejo-Borbolla, A., Schulz, T. F. (2006). Kaposi's Sarcoma-Associated Herpesvirus LANA-1 Interacts with the Short Variant of BRD4 and Releases Cells from a BRD4- and BRD2/RING3-Induced G1 Cell Cycle Arrest. J. Virol. 80: 10772-10786 [Abstract] [Full Text]  
  • McPhillips, M. G., Oliveira, J. G., Spindler, J. E., Mitra, R., McBride, A. A. (2006). Brd4 Is Required for E2-Mediated Transcriptional Activation but Not Genome Partitioning of All Papillomaviruses. J. Virol. 80: 9530-9543 [Abstract] [Full Text]  
  • Zhou, Q., Yik, J. H. N. (2006). The Yin and Yang of P-TEFb Regulation: Implications for Human Immunodeficiency Virus Gene Expression and Global Control of Cell Growth and Differentiation. Microbiol. Mol. Biol. Rev. 70: 646-659 [Abstract] [Full Text]  
  • You, J., Srinivasan, V., Denis, G. V., Harrington, W. J. Jr., Ballestas, M. E., Kaye, K. M., Howley, P. M. (2006). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Interacts with Bromodomain Protein Brd4 on Host Mitotic Chromosomes.. J. Virol. 80: 8909-8919 [Abstract] [Full Text]  
  • Wu, S.-Y., Lee, A-Y., Hou, S. Y., Kemper, J. K., Erdjument-Bromage, H., Tempst, P., Chiang, C.-M. (2006). Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev. 20: 2383-2396 [Abstract] [Full Text]  
  • Schweiger, M.-R., You, J., Howley, P. M. (2006). Bromodomain Protein 4 Mediates the Papillomavirus E2 Transcriptional Activation Function. J. Virol. 80: 4276-4285 [Abstract] [Full Text]  
  • Nishiyama, A., Dey, A., Miyazaki, J.-i., Ozato, K. (2006). Brd4 Is Required for Recovery from Antimicrotubule Drug-induced Mitotic Arrest: Preservation of Acetylated Chromatin. Mol. Biol. Cell 17: 814-823 [Abstract] [Full Text]  
  • Oliveira, J. G., Colf, L. A., McBride, A. A. (2006). Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc. Natl. Acad. Sci. USA 103: 1047-1052 [Abstract] [Full Text]  
  • You, J., Schweiger, M.-R., Howley, P. M. (2005). Inhibition of E2 Binding to Brd4 Enhances Viral Genome Loss and Phenotypic Reversion of Bovine Papillomavirus-Transformed Cells. J. Virol. 79: 14956-14961 [Abstract] [Full Text]  
  • Janvier, K., Bonifacino, J. S. (2005). Role of the Endocytic Machinery in the Sorting of Lysosome-associated Membrane Proteins. Mol. Biol. Cell 16: 4231-4242 [Abstract] [Full Text]  
  • McPhillips, M. G., Ozato, K., McBride, A. A. (2005). Interaction of Bovine Papillomavirus E2 Protein with Brd4 Stabilizes Its Association with Chromatin. J. Virol. 79: 8920-8932 [Abstract] [Full Text]  
  • Haruki, N, Kawaguchi, K S, Eichenberger, S, Massion, P P, Gonzalez, A, Gazdar, A F, Minna, J D, Carbone, D P, Dang, T P (2005). Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro. J. Med. Genet. 42: 558-564 [Abstract] [Full Text]  
  • Baxter, M. K., McPhillips, M. G., Ozato, K., McBride, A. A. (2005). The Mitotic Chromosome Binding Activity of the Papillomavirus E2 Protein Correlates with Interaction with the Cellular Chromosomal Protein, Brd4. J. Virol. 79: 4806-4818 [Abstract] [Full Text]  
  • Brannon, A. R., Maresca, J. A., Boeke, J. D., Basrai, M. A., McBride, A. A. (2005). Reconstitution of papillomavirus E2-mediated plasmid maintenance in Saccharomyces cerevisiae by the Brd4 bromodomain protein. Proc. Natl. Acad. Sci. USA 102: 2998-3003 [Abstract] [Full Text]  
  • French, C. A., Kutok, J. L., Faquin, W. C., Toretsky, J. A., Antonescu, C. R., Griffin, C. A., Nose, V., Vargas, S. O., Moschovi, M., Tzortzatou-Stathopoulou, F., Miyoshi, I., Perez-Atayde, A. R., Aster, J. C., Fletcher, J. A. (2004). Midline Carcinoma of Children and Young Adults With NUT Rearrangement. JCO 22: 4135-4139 [Abstract] [Full Text]  
  • Farina, A., Hattori, M., Qin, J., Nakatani, Y., Minato, N., Ozato, K. (2004). Bromodomain Protein Brd4 Binds to GTPase-Activating SPA-1, Modulating Its Activity and Subcellular Localization. Mol. Cell. Biol. 24: 9059-9069 [Abstract] [Full Text]  
  • Kutney, S. N., Hong, R., Macfarlan, T., Chakravarti, D. (2004). A Signaling Role of Histone-binding Proteins and INHAT Subunits pp32 and Set/TAF-I{beta} in Integrating Chromatin Hypoacetylation and Transcriptional Repression. J. Biol. Chem. 279: 30850-30855 [Abstract] [Full Text]  
  • Greenwald, R. J., Tumang, J. R., Sinha, A., Currier, N., Cardiff, R. D., Rothstein, T. L., Faller, D. V., Denis, G. V. (2004). E{micro}-BRD2 transgenic mice develop B-cell lymphoma and leukemia. Blood 103: 1475-1484 [Abstract] [Full Text]  
  • Janvier, K., Kato, Y., Boehm, M., Rose, J. R., Martina, J. A., Kim, B.-Y., Venkatesan, S., Bonifacino, J. S. (2003). Recognition of dileucine-based sorting signals from HIV-1 Nef and LIMP-II by the AP-1 {gamma}-{sigma}1 and AP-3 {delta}-{sigma}3 hemicomplexes. JCB 163: 1281-1290 [Abstract] [Full Text]  
  • Pivot-Pajot, C., Caron, C., Govin, J., Vion, A., Rousseaux, S., Khochbin, S. (2003). Acetylation-Dependent Chromatin Reorganization by BRDT, a Testis-Specific Bromodomain-Containing Protein. Mol. Cell. Biol. 23: 5354-5365 [Abstract] [Full Text]  
  • Dey, A., Chitsaz, F., Abbasi, A., Misteli, T., Ozato, K. (2003). The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. Proc. Natl. Acad. Sci. USA 100: 8758-8763 [Abstract] [Full Text]  
  • Viejo-Borbolla, A., Kati, E., Sheldon, J. A., Nathan, K., Mattsson, K., Szekely, L., Schulz, T. F. (2003). A Domain in the C-Terminal Region of Latency-Associated Nuclear Antigen 1 of Kaposi's Sarcoma-Associated Herpesvirus Affects Transcriptional Activation and Binding to Nuclear Heterochromatin. J. Virol. 77: 7093-7100 [Abstract] [Full Text]  
  • French, C. A., Miyoshi, I., Kubonishi, I., Grier, H. E., Perez-Atayde, A. R., Fletcher, J. A. (2003). BRD4-NUT Fusion Oncogene: A Novel Mechanism in Aggressive Carcinoma. Cancer Res. 63: 304-307 [Abstract] [Full Text]  
  • Maruyama, T., Farina, A., Dey, A., Cheong, J., Bermudez, V. P., Tamura, T., Sciortino, S., Shuman, J., Hurwitz, J., Ozato, K. (2002). A Mammalian Bromodomain Protein, Brd4, Interacts with Replication Factor C and Inhibits Progression to S Phase. Mol. Cell. Biol. 22: 6509-6520 [Abstract] [Full Text]  
  • Crowley, T. E., Kaine, E. M., Yoshida, M., Nandi, A., Wolgemuth, D. J. (2002). Reproductive Cycle Regulation of Nuclear Import, Euchromatic Localization, and Association with Components of Pol II Mediator of a Mammalian Double-Bromodomain Protein. Mol. Endocrinol. 16: 1727-1737 [Abstract] [Full Text]  
  • Houzelstein, D., Bullock, S. L., Lynch, D. E., Grigorieva, E. F., Wilson, V. A., Beddington, R. S. P. (2002). Growth and Early Postimplantation Defects in Mice Deficient for the Bromodomain-Containing Protein Brd4{dagger}. Mol. Cell. Biol. 22: 3794-3802 [Abstract] [Full Text]  
  • Mattsson, K., Kiss, C., Platt, G. M., Simpson, G. R., Kashuba, E., Klein, G., Schulz, T. F., Szekely, L. (2002). Latent nuclear antigen of Kaposi's sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions. J. Gen. Virol. 83: 179-188 [Abstract] [Full Text]  
  • Chen, D., Hinkley, C. S., Henry, R. W., Huang, S. (2002). TBP Dynamics in Living Human Cells: Constitutive Association of TBP with Mitotic Chromosomes. Mol. Biol. Cell 13: 276-284 [Abstract] [Full Text]  
  • French, C. A., Miyoshi, I., Aster, J. C., Kubonishi, I., Kroll, T. G., Dal Cin, P., Vargas, S. O., Perez-Atayde, A. R., Fletcher, J. A. (2001). BRD4 Bromodomain Gene Rearrangement in Aggressive Carcinoma with Translocation t(15;19). Am. J. Pathol. 159: 1987-1992 [Abstract] [Full Text]  
  • Kimura, H., Cook, P. R. (2001). Kinetics of Core Histones in Living Human Cells: Little Exchange of H3 and H4 and Some Rapid Exchange of H2B. JCB 153: 1341-1354 [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»