p21WAF-1 reorganizes the nucleus in tumor suppression

被引:51
作者
Linares-Cruz, G
Bruzzoni-Giovanelli, H
Alvaro, V
Roperch, JP
Tuynder, M
Schoevaert, D
Nemani, M
Prieur, S
Lethrosne, F
Piouffre, L
Reclar, V
Faille, A
Chassoux, D
Dausset, J
Amson, RB
Calvo, F
Telerman, A
机构
[1] Fdn Jean Dausset, CEPH, F-75010 Paris, France
[2] Inst Genet Mol, Lab Pharmacol Expt, F-75010 Paris, France
[3] Free Univ Brussels, Dept Biol Mol, B-1640 Rhode St Genese, Belgium
[4] Hop St Louis, Lab Anal Images Pathol Cellulaire, F-75010 Paris, France
[5] Inst Biol Physico Chim, INSERM U310, F-75005 Paris, France
关键词
cancer genetics; chromatin architecture; genome organization; p53;
D O I
10.1073/pnas.95.3.1131
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Interphasic nuclear organization has a key function in genome biology, We demonstrate that p21(WAF-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 p21(WAF-1) resulted in expression of the HUMSIAH (human seven in absentia homologue), Rb, and Rbr-2 genes and strong suppression of the malignant phenotype. p21(WAF-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.
引用
收藏
页码:1131 / 1135
页数:5
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