QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Filesi, I. Articles by Biocca, S. Search for Related Content PubMed PubMed Citation Articles by Filesi, I. Articles by Biocca, S. Social Bookmarking                         What's this?

Loss of Heterochromatin Protein 1 (HP1) chromodomain function in mammalian cells by intracellular antibodies causes cell death

¹ Department of Neuroscience, University of Roma, Tor Vergata, Via Montpellier 1, 00133 Roma, Italy
² Nuclear Reprogramming Laboratory, Division of Gene Expression and Development, Roslin Institute (Edinburgh), Midlothian, Scotland, EH25 9PS, UK

^* Authors for correspondence (e-mail: biocca{at}med.uniroma2.it and prim.singh{at}bbsrc.ac.uk )

Accepted 1 February 2002

The chromodomain (CD) is a highly conserved motif present in a variety of animal and plant proteins, and its probable role is to assemble a variety of macromolecular complexes in chromatin. The importance of the CD to the survival of mammalian cells has been tested. Accordingly, we have ablated CD function using two single-chain intracellular Fv (scFv) fragments directed against non-overlapping epitopes within the HP1 CD motif. The scFv fragments can recognize both CD motifs of HP1 and Polycomb (Pc) in vitro and, when expressed intracellularly, interact with and dislodge the HP1 protein(s) from their heterochromatin localization in vivo. Mouse and human fibroblasts expressing anti-chromodomain scFv fragments show a cell-lethal phenotype and an apoptotic morphology becomes apparent soon after transfection. The mechanism of cell death appears to be p53 independent, and the cells are only partly rescued by incubation with the wide spectrum caspase inhibitor Z-VAD fmk. We conclude that expression of anti-chromodomain intracellular antibodies is sufficient to trigger a p53-independent apoptotic pathway that is only partly dependent on the known Z-VAD-inhibitable caspases, suggesting that CD function is essential for cell survival.

Key words: Intracellular antibodies, scFv fragments, Chromodomain, HP1 proteins, Heterochromatin, Apoptosis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. S. Luijsterburg, C. Dinant, H. Lans, J. Stap, E. Wiernasz, S. Lagerwerf, D. O. Warmerdam, M. Lindh, M. C. Brink, J. W. Dobrucki, et al. Heterochromatin protein 1 is recruited to various types of DNA damage J. Cell Biol., May 18, 2009; 185(4): 577 - 586. [Abstract] [Full Text] [PDF]

				G. K. Dialynas, S. Terjung, J. P. Brown, R. L. Aucott, B. Baron-Luhr, P. B. Singh, and S. D. Georgatos Plasticity of HP1 proteins in mammalian cells J. Cell Sci., October 1, 2007; 120(19): 3415 - 3424. [Abstract] [Full Text] [PDF]

				E. Ritou, M. Bai, and S. D. Georgatos Variant-specific patterns and humoral regulation of HP1 proteins in human cells and tissues J. Cell Sci., October 1, 2007; 120(19): 3425 - 3435. [Abstract] [Full Text] [PDF]

				M. Kaller, U. Euteneuer, and W. Nellen Differential Effects of Heterochromatin Protein 1 Isoforms on Mitotic Chromosome Distribution and Growth in Dictyostelium discoideum Eukaryot. Cell, March 1, 2006; 5(3): 530 - 543. [Abstract] [Full Text] [PDF]

				R. Mango, S. Biocca, F. del Vecchio, F. Clementi, F. Sangiuolo, F. Amati, A. Filareto, S. Grelli, P. Spitalieri, I. Filesi, et al. In Vivo and In Vitro Studies Support That a New Splicing Isoform of OLR1 Gene Is Protective Against Acute Myocardial Infarction Circ. Res., July 22, 2005; 97(2): 152 - 158. [Abstract] [Full Text] [PDF]