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 Zhang, Z.-K.
Right arrow Articles by Kalpana, G. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, Z.-K.
Right arrow Articles by Kalpana, G. V.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2002, p. 5975-5988, Vol. 22, No. 16
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.16.5975-5988.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cell Cycle Arrest and Repression of Cyclin D1 Transcription by INI1/hSNF5

Zhi-Kai Zhang,1 Kelvin P. Davies,1 Jeffrey Allen,2 Liang Zhu,3 Richard G. Pestell,3,4 David Zagzag,5 and Ganjam V. Kalpana1*

Departments of Molecular Genetics,1 Developmental and Molecular Biology,3 Medicine, Albert Einstein College of Medicine, Bronx,4 The Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, North Division,2 Department of Pathology, New York University Medical School, New York, New York5

Received 4 February 2002/ Returned for modification 18 March 2002/ Accepted 3 May 2002

INI1/hSNF5 is a component of the ATP-dependent chromatin remodeling hSWI/SNF complex and a tumor suppressor gene of aggressive pediatric atypical teratoid and malignant rhabdoid tumors (AT/RT). To understand the molecular mechanisms underlying its tumor suppressor function, we studied the effect of reintroduction of INI1/hSNF5 into AT/RT-derived cell lines such as MON that carry biallelic deletions of the INI1/hSNF5 locus. We demonstrate that expression of INI1/hSNF5 causes G0-G1 arrest and flat cell formation in these cells. In addition, INI1/hSNF5 repressed transcription of cyclin D1 gene in MON, in a histone deacetylase (HDAC)-dependent manner. Chromatin immunoprecipitation studies revealed that INI1/hSNF5 was directly recruited to the cyclin D1 promoter and that its binding correlated with recruitment of HDAC1 and deacetylation of histones at the promoter. Analysis of INI1/hSNF5 truncations indicated that cyclin D1 repression and flat cell formation are tightly correlated. Coexpression of cyclin D1 from a heterologous promoter in MON was sufficient to eliminate the INI1-mediated flat cell formation and cell cycle arrest. Furthermore, cyclin D1 was overexpressed in AT/RT tumors. Our data suggest that one of the mechanisms by which INI1/hSNF5 exerts its tumor suppressor function is by mediating the cell cycle arrest due to the direct recruitment of HDAC activity to the cyclin D1 promoter thereby causing its repression and G0-G1 arrest. Repression of cyclin D1 gene expression may serve as a useful strategy to treat AT/RT.

* Corresponding author. Mailing address: Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., U821, Bronx, NY 10461. Phone (718) 430-2354. Fax (718) 430-8778. E-mail: kalpana{at}aecom.yu.edu.

Molecular and Cellular Biology, August 2002, p. 5975-5988, Vol. 22, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.16.5975-5988.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chandrasekaran, S., Peterson, R. E., Mani, S. K., Addy, B., Buchholz, A. L., Xu, L., Thiyagarajan, T., Kasiganesan, H., Kern, C. B., Menick, D. R. (2009). Histone deacetylases facilitate sodium/calcium exchanger up-regulation in adult cardiomyocytes. FASEB J. 23: 3851-3864 [Abstract] [Full Text]  
  • Wang, X., Sansam, C. G., Thom, C. S., Metzger, D., Evans, J. A., Nguyen, P. T.L., Roberts, C. W.M. (2009). Oncogenesis Caused by Loss of the SNF5 Tumor Suppressor Is Dependent on Activity of BRG1, the ATPase of the SWI/SNF Chromatin Remodeling Complex. Cancer Res. 69: 8094-8101 [Abstract] [Full Text]  
  • Muntean, A. G., Hess, J. L. (2009). Epigenetic Dysregulation in Cancer. Am. J. Pathol. 175: 1353-1361 [Abstract] [Full Text]  
  • Zhou, R., Han, L., Li, G., Tong, T. (2009). Senescence delay and repression of p16INK4a by Lsh via recruitment of histone deacetylases in human diploid fibroblasts. Nucleic Acids Res 37: 5183-5196 [Abstract] [Full Text]  
  • Swensen, J J, Keyser, J, Coffin, C M, Biegel, J A, Viskochil, D H, Williams, M S (2009). Familial occurrence of schwannomas and malignant rhabdoid tumour associated with a duplication in SMARCB1. J. Med. Genet. 46: 68-72 [Abstract] [Full Text]  
  • McKenna, E. S., Sansam, C. G., Cho, Y.-J., Greulich, H., Evans, J. A., Thom, C. S., Moreau, L. A., Biegel, J. A., Pomeroy, S. L., Roberts, C. W. M. (2008). Loss of the Epigenetic Tumor Suppressor SNF5 Leads to Cancer without Genomic Instability. Mol. Cell. Biol. 28: 6223-6233 [Abstract] [Full Text]  
  • Caramel, J., Quignon, F., Delattre, O. (2008). RhoA-Dependent Regulation of Cell Migration by the Tumor Suppressor hSNF5/INI1. Cancer Res. 68: 6154-6161 [Abstract] [Full Text]  
  • Smith, M. E., Cimica, V., Chinni, S., Challagulla, K., Mani, S., Kalpana, G. V. (2008). Rhabdoid Tumor Growth is Inhibited by Flavopiridol. Clin. Cancer Res. 14: 523-532 [Abstract] [Full Text]  
  • Huerta, M., Munoz, R., Tapia, R., Soto-Reyes, E., Ramirez, L., Recillas-Targa, F., Gonzalez-Mariscal, L., Lopez-Bayghen, E. (2007). Cyclin D1 Is Transcriptionally Down-Regulated by ZO-2 via an E Box and the Transcription Factor c-Myc. Mol. Biol. Cell 18: 4826-4836 [Abstract] [Full Text]  
  • Das, A. V., James, J., Bhattacharya, S., Imbalzano, A. N., Antony, M. L., Hegde, G., Zhao, X., Mallya, K., Ahmad, F., Knudsen, E., Ahmad, I. (2007). SWI/SNF Chromatin Remodeling ATPase Brm Regulates the Differentiation of Early Retinal Stem Cells/Progenitors by Influencing Brn3b Expression and Notch Signaling. J. Biol. Chem. 282: 35187-35201 [Abstract] [Full Text]  
  • Morozov, A., Lee, S. J., Zhang, Z.-K., Cimica, V., Zagzag, D., Kalpana, G. V. (2007). INI1 Induces Interferon Signaling and Spindle Checkpoint in Rhabdoid Tumors. Clin. Cancer Res. 13: 4721-4730 [Abstract] [Full Text]  
  • Zraly, C. B., Middleton, F. A., Dingwall, A. K. (2006). Hormone-response Genes Are Direct in Vivo Regulatory Targets of Brahma (SWI/SNF) Complex Function. J. Biol. Chem. 281: 35305-35315 [Abstract] [Full Text]  
  • Guidi, C. J., Mudhasani, R., Hoover, K., Koff, A., Leav, I., Imbalzano, A. N., Jones, S. N. (2006). Functional Interaction of the Retinoblastoma and Ini1/Snf5 Tumor Suppressors in Cell Growth and Pituitary Tumorigenesis. Cancer Res. 66: 8076-8082 [Abstract] [Full Text]  
  • Klochendler-Yeivin, A., Picarsky, E., Yaniv, M. (2006). Increased DNA Damage Sensitivity and Apoptosis in Cells Lacking the Snf5/Ini1 Subunit of the SWI/SNF Chromatin Remodeling Complex.. Mol. Cell. Biol. 26: 2661-2674 [Abstract] [Full Text]  
  • Nagl, N. G. Jr., Zweitzig, D. R., Thimmapaya, B., Beck, G. R. Jr., Moran, E. (2006). The c-myc Gene Is a Direct Target of Mammalian SWI/SNF-Related Complexes during Differentiation-Associated Cell Cycle Arrest. Cancer Res. 66: 1289-1293 [Abstract] [Full Text]  
  • Hartman, S. E., Bertone, P., Nath, A. K., Royce, T. E., Gerstein, M., Weissman, S., Snyder, M. (2005). Global changes in STAT target selection and transcription regulation upon interferon treatments. Genes Dev. 19: 2953-2968 [Abstract] [Full Text]  
  • Isakoff, M. S., Sansam, C. G., Tamayo, P., Subramanian, A., Evans, J. A., Fillmore, C. M., Wang, X., Biegel, J. A., Pomeroy, S. L., Mesirov, J. P., Roberts, C. W. M. (2005). Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Proc. Natl. Acad. Sci. USA 102: 17745-17750 [Abstract] [Full Text]  
  • Rampalli, S., Pavithra, L., Bhatt, A., Kundu, T. K., Chattopadhyay, S. (2005). Tumor Suppressor SMAR1 Mediates Cyclin D1 Repression by Recruitment of the SIN3/Histone Deacetylase 1 Complex. Mol. Cell. Biol. 25: 8415-8429 [Abstract] [Full Text]  
  • Tsikitis, M., Zhang, Z., Edelman, W., Zagzag, D., Kalpana, G. V. (2005). Genetic ablation of Cyclin D1 abrogates genesis of rhabdoid tumors resulting from Ini1 loss. Proc. Natl. Acad. Sci. USA 102: 12129-12134 [Abstract] [Full Text]  
  • Hilton, T. L., Li, Y., Dunphy, E. L., Wang, E. H. (2005). TAF1 Histone Acetyltransferase Activity in Sp1 Activation of the Cyclin D1 Promoter. Mol. Cell. Biol. 25: 4321-4332 [Abstract] [Full Text]  
  • Vries, R. G.J., Bezrookove, V., Zuijderduijn, L. M.P., Kia, S. K., Houweling, A., Oruetxebarria, I., Raap, A. K., Verrijzer, C. P. (2005). Cancer-associated mutations in chromatin remodeler hSNF5 promote chromosomal instability by compromising the mitotic checkpoint. Genes Dev. 19: 665-670 [Abstract] [Full Text]  
  • Tekautz, T. M., Fuller, C. E., Blaney, S., Fouladi, M., Broniscer, A., Merchant, T. E., Krasin, M., Dalton, J., Hale, G., Kun, L. E., Wallace, D., Gilbertson, R. J., Gajjar, A. (2005). Atypical Teratoid/Rhabdoid Tumors (ATRT): Improved Survival in Children 3 Years of Age and Older With Radiation Therapy and High-Dose Alkylator-Based Chemotherapy. JCO 23: 1491-1499 [Abstract] [Full Text]  
  • Zraly, C. B., Marenda, D. R., Dingwall, A. K. (2004). SNR1 (INI1/SNF5) Mediates Important Cell Growth Functions of the Drosophila Brahma (SWI/SNF) Chromatin Remodeling Complex. Genetics 168: 199-214 [Abstract] [Full Text]  
  • D'Amico, M., Wu, K., Fu, M., Rao, M., Albanese, C., Russell, R. G., Lian, H., Bregman, D., White, M. A., Pestell, R. G. (2004). The Inhibitor of Cyclin-Dependent Kinase 4a/Alternative Reading Frame (INK4a/ARF) Locus Encoded Proteins p16INK4a and p19ARF Repress Cyclin D1 Transcription through Distinct cis Elements. Cancer Res. 64: 4122-4130 [Abstract] [Full Text]  
  • Medjkane, S., Novikov, E., Versteege, I., Delattre, O. (2004). The Tumor Suppressor hSNF5/INI1 Modulates Cell Growth and Actin Cytoskeleton Organization. Cancer Res. 64: 3406-3413 [Abstract] [Full Text]  
  • Arco, P. G.-d., Maki, K., Georgopoulos, K. (2004). Phosphorylation Controls Ikaros's Ability To Negatively Regulate the G1-S Transition. Mol. Cell. Biol. 24: 2797-2807 [Abstract] [Full Text]  
  • Guidi, C. J., Veal, T. M., Jones, S. N., Imbalzano, A. N. (2004). Transcriptional Compensation for Loss of an Allele of the Ini1 Tumor Suppressor. J. Biol. Chem. 279: 4180-4185 [Abstract] [Full Text]  
  • Kang, H., Cui, K., Zhao, K. (2004). BRG1 Controls the Activity of the Retinoblastoma Protein via Regulation of p21CIP1/WAF1/SDI. Mol. Cell. Biol. 24: 1188-1199 [Abstract] [Full Text]  
  • Oruetxebarria, I., Venturini, F., Kekarainen, T., Houweling, A., Zuijderduijn, L. M. P., Mohd-Sarip, A., Vries, R. G. J., Hoeben, R. C., Verrijzer, C. P. (2004). p16INK4a Is Required for hSNF5 Chromatin Remodeler-induced Cellular Senescence in Malignant Rhabdoid Tumor Cells. J. Biol. Chem. 279: 3807-3816 [Abstract] [Full Text]  
  • Pal, S., Yun, R., Datta, A., Lacomis, L., Erdjument-Bromage, H., Kumar, J., Tempst, P., Sif, S. (2003). mSin3A/Histone Deacetylase 2- and PRMT5-Containing Brg1 Complex Is Involved in Transcriptional Repression of the Myc Target Gene cad. Mol. Cell. Biol. 23: 7475-7487 [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»