p21WAF-1 reorganizes the nucleus in tumor suppression.
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. 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.
Linares-Cruz
G
G
Laboratoire de Pharmacologie Expérimentale, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, 75010 Paris, France.
Bruzzoni-Giovanelli
H
H
Alvaro
V
V
Roperch
J P
JP
Tuynder
M
M
Schoevaert
D
D
Nemani
M
M
Prieur
S
S
Lethrosne
F
F
Piouffre
L
L
Reclar
V
V
Faille
A
A
Chassoux
D
D
Dausset
J
J
Amson
R B
RB
Calvo
F
F
Telerman
A
A
D002467:Cell Nucleus / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002875:Chromosomes / Q000502:physiology*; D002882:Chromosomes, Human, Pair 13 / Q000502:physiology; D002885:Chromosomes, Human, Pair 16 / Q000502:physiology; D002886:Chromosomes, Human, Pair 17 / Q000502:physiology; D002891:Chromosomes, Human, Pair 21 / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D003850:Deoxyribonuclease I / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009687:Nuclear Proteins; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics; D050717:Retinoblastoma-Like Protein p130; D014162:Transfection; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493837:RBL2 protein, human; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D003850:Deoxyribonuclease I