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| Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence |
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| Author(s): Narita M, Nunez S, Heard E, Narita M, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW |
| Source: CELL Volume: 113 Issue: 6 Pages: 703-716 Published: JUN 13 2003 |
| Times Cited: 388 References: 52 |
| Abstract: Cellular senescence is an extremely stable form of cell cycle arrest that limits the proliferation of damaged cells and may act as a natural barrier to cancer progression. In this study, we describe a distinct heterochromatic structure that accumulates in senescent human fibroblasts, which we designated senescence-associated heterochromatic foci (SAHF). SAHF formation coincides with the recruitment of heterochromatin proteins and the retinoblastoma (Rb) tumor suppressor to E2F-responsive promoters and is associated with the stable repression of E2F target genes. Notably, both SAHF formation and the silencing of E2F target genes depend on the integrity of the Rb pathway and do not occur in reversibly arrested cells. These results provide a molecular explanation for the stability of the senescent state, as well as new insights into the action of Rb as a tumor suppressor. |
| Document Type: Article |
| Language: English |
| Reprint Address: Lowe, SW (reprint author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA |
Addresses:
1. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
2. SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA
3. Inst Curie, CNRS, UMR 218, F-75248 Paris, France |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 689VV |
| ISSN: 0092-8674 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |