p21WAF-1 reorganizes the nucleus in tumor suppression
- Gustavo Linares-Cruz*,
- Heriberto Bruzzoni-Giovanelli*,
- Véronique Alvaro†,
- Jean-Pierre Roperch†,
- Marcel Tuynder‡,
- Damien Schoevaert§,
- Mona Nemani†,
- Sylvie Prieur†,
- Florence Lethrosne†,
- Laurence Piouffre†,
- Valérie Reclar*,
- Annick Faille*,
- Danièle Chassoux¶,
- Jean Dausset†,
- Robert B. Amson†,
- Fabien Calvo*, and
- Adam Telerman†‖
- *Laboratoire de Pharmacologie Expérimentale, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, 75010 Paris, France; †Fondation Jean Dausset, Centre d’Etude du Polymorphisme Humain (CEPH), 27 rue Juliette Dodu, 75010 Paris, France; ‡Department of Molecular Biology, Free University of Brussels, 67, rue des Chevaux, 1640 Rhode St Genèse, Belgium; §Laboratoire d’Analyse d’Images en Pathologie Cellulaire, Hôpital St Louis, 1, Avenue Claude Vellefaux, 75010 Paris Paris, France; and ¶Unité 310 Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Physico Chimie, 13 rue Pierre et Marie Curie, 75005 Paris, France
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Communicated by Georges Charpak, European Organization for Nuclear Research, Geneva, Switzerland (received for review June 24, 1997)
Abstract
Interphasic nuclear organization has a key function in genome biology. We demonstrate that p21WAF-1, by influencing gene expression and inducing chromosomal repositioning in tumor suppression, plays a major role as a nuclear organizer. Transfection of U937 tumor cells with p21WAF-1 resulted in expression of the HUMSIAH (human seven in absentia homologue), Rb, and Rbr-2 genes and strong suppression of the malignant phenotype. p21WAF-1 drastically modified the compartmentalization of the nuclear genome. DNase I genome exposure and fluorescence in situ hybridization show, respectively, a displacement of the sensitive sites to the periphery of the nucleus and repositioning of chromosomes 13, 16, 17, and 21. These findings, addressing nuclear architecture modulations, provide potentially significant perspectives for the understanding of tumor suppression.
ABBREVIATIONS
- HUMSIAH,
- human seven in absentia homologue;
- FISH,
- fluorescent in situ hybridization
- Received June 24, 1997.
- Accepted July 25, 1997.
- Copyright © 1998, The National Academy of Sciences
