This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Citterio, E. Articles by Bonapace, I. M. Search for Related Content PubMed PubMed Citation Articles by Citterio, E. Articles by Bonapace, I. M.

Np95 Is a Histone-Binding Protein Endowed with Ubiquitin Ligase Activity

Elisabetta Citterio,^1,2, Roberto Papait,^1,3, Francesco Nicassio,^1,2 Manuela Vecchi,¹ Paola Gomiero,³ Roberto Mantovani,⁴ Pier Paolo Di Fiore,^1,2,5* and Ian Marc Bonapace^1,3

Istituto FIRC di Oncologia Molecolare, 20139 Milan,¹ Istituto Europeo di Oncologia, 20141 Milan,² Dipartimento di Biologia Strutturale e Funzionale, Università dell'Insubria, 21502 Varese,³ Dipartimento di Genetica e Biologia dei Microorganismi, Università degli Studi di Milano, 20133 Milan,⁴ Dipartimento di Medicina, Chirurgia ed Odontoiatria, Università di Milano, 20112 Milan, Italy⁵

Received 1 October 2003/ Returned for modification 9 November 2003/ Accepted 9 December 2003

Np95 is an important determinant in cell cycle progression. Its expression is tightly regulated and becomes detectable shortly before the entry of cells into S phase. Accordingly, Np95 is absolutely required for the G₁/S transition. Its continued expression throughout the S/G₂/M phases further suggests additional roles. Indeed, Np95 has been implicated in DNA damage response. Here, we show that Np95 is tightly bound to chromatin in vivo and that it binds to histones in vivo and in vitro. The binding to histones is direct and shows a remarkable preference for histone H3 and its N-terminal tail. A novel protein domain, the SRA-YDG domain, contained in Np95 is indispensable both for the interaction with histones and for chromatin binding in vivo. Np95 contains a RING finger. We show that this domain confers E3 ubiquitin ligase activity on Np95, which is specific for core histones, in vitro. Finally, Np95 shows specific E3 activity for histone H3 when the endogenous core octamer, coimmunoprecipitating with Np95, is used as a substrate. Histone ubiquitination is an important determinant in the regulation of chromatin structure and gene transcription. Thus, the demonstration that Np95 is a chromatin-associated ubiquitin ligase suggests possible molecular mechanisms for its action as a cell cycle regulator.

E.C. and R.P. contributed equally to this work.

This article has been cited by other articles:

• Karagianni, P., Amazit, L., Qin, J., Wong, J. (2008). ICBP90, a Novel Methyl K9 H3 Binding Protein Linking Protein Ubiquitination with Heterochromatin Formation. Mol. Cell. Biol. 28: 705-717 [Abstract] [Full Text]  
• Hastie, A. R., Pruitt, S. C. (2007). Yeast two-hybrid interaction partner screening through in vivo Cre-mediated Binary Interaction Tag generation. Nucleic Acids Res 35: e141-e141 [Abstract] [Full Text]  
• Bostick, M., Kim, J. K., Esteve, P.-O., Clark, A., Pradhan, S., Jacobsen, S. E. (2007). UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells. Science 317: 1760-1764 [Abstract] [Full Text]  
• van den Boom, V., Kooistra, S. M., Boesjes, M., Geverts, B., Houtsmuller, A. B., Monzen, K., Komuro, I., Essers, J., Drenth-Diephuis, L. J., Eggen, B. J.L. (2007). UTF1 is a chromatin-associated protein involved in ES cell differentiation. J. Cell Biol. 178: 913-924 [Abstract] [Full Text]  
• Papait, R., Pistore, C., Negri, D., Pecoraro, D., Cantarini, L., Bonapace, I. M. (2007). Np95 Is Implicated in Pericentromeric Heterochromatin Replication and in Major Satellite Silencing. Mol. Biol. Cell 18: 1098-1106 [Abstract] [Full Text]  
• Woo, H. R., Pontes, O., Pikaard, C. S., Richards, E. J. (2007). VIM1, a methylcytosine-binding protein required for centromeric heterochromatinization. Genes Dev. 21: 267-277 [Abstract] [Full Text]  
• Sadler, K. C., Krahn, K. N., Gaur, N. A., Ukomadu, C. (2007). Liver growth in the embryo and during liver regeneration in zebrafish requires the cell cycle regulator, uhrf1. Proc. Natl. Acad. Sci. USA 104: 1570-1575 [Abstract] [Full Text]  
• Casas-Mollano, J. A., Lao, N. T., Kavanagh, T. A. (2006). Intron-regulated expression of SUVH3, an Arabidopsis Su(var)3-9 homologue. J Exp Bot 57: 3301-3311 [Abstract] [Full Text]  
• Jenkins, Y., Markovtsov, V., Lang, W., Sharma, P., Pearsall, D., Warner, J., Franci, C., Huang, B., Huang, J., Yam, G. C., Vistan, J. P., Pali, E., Vialard, J., Janicot, M., Lorens, J. B., Payan, D. G., Hitoshi, Y. (2005). Critical Role of the Ubiquitin Ligase Activity of UHRF1, a Nuclear RING Finger Protein, in Tumor Cell Growth. Mol. Biol. Cell 16: 5621-5629 [Abstract] [Full Text]  
• Liu, Z., Oughtred, R., Wing, S. S. (2005). Characterization of E3Histone, a Novel Testis Ubiquitin Protein Ligase Which Ubiquitinates Histones. Mol. Cell. Biol. 25: 2819-2831 [Abstract] [Full Text]  
• Stone, S. L., Hauksdottir, H., Troy, A., Herschleb, J., Kraft, E., Callis, J. (2005). Functional Analysis of the RING-Type Ubiquitin Ligase Family of Arabidopsis. Plant Physiol. 137: 13-30 [Abstract] [Full Text]  
• Frazier, T., Shakes, D., Hota, U., Boyd, L. (2004). Caenorhabditis elegans UBC-2 functions with the anaphase-promoting complex but also has other activities. J. Cell Sci. 117: 5427-5435 [Abstract] [Full Text]