PMID- 12809602
OWN - NLM
STAT- MEDLINE
DCOM- 20030723
LR  - 20220318
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 113
IP  - 6
DP  - 2003 Jun 13
TI  - Rb-mediated heterochromatin formation and silencing of E2F target genes during 
      cellular senescence.
PG  - 703-16
AB  - 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.
FAU - Narita, Masashi
AU  - Narita M
AD  - Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, 
      USA.
FAU - Nunez, Sabrina
AU  - Nunez S
FAU - Heard, Edith
AU  - Heard E
FAU - Narita, Masako
AU  - Narita M
FAU - Lin, Athena W
AU  - Lin AW
FAU - Hearn, Stephen A
AU  - Hearn SA
FAU - Spector, David L
AU  - Spector DL
FAU - Hannon, Gregory J
AU  - Hannon GJ
FAU - Lowe, Scott W
AU  - Lowe SW
LA  - eng
GR  - CA13106/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - GM42694/GM/NIGMS NIH HHS/United States
GR  - AG16379/AG/NIA NIH HHS/United States
GR  - R01 GM042694/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F Transcription Factors)
RN  - 0 (Heterochromatin)
RN  - 0 (Repressor Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Binding Sites/genetics
MH  - *Cell Cycle Proteins
MH  - Cell Line
MH  - Cell Size/genetics
MH  - Cellular Senescence/*genetics
MH  - DNA/genetics/metabolism
MH  - *DNA-Binding Proteins
MH  - E2F Transcription Factors
MH  - Eukaryotic Cells/*metabolism/ultrastructure
MH  - Fibroblasts/metabolism/ultrastructure
MH  - Gene Silencing/*physiology
MH  - Gene Targeting
MH  - Genes, p16/physiology
MH  - Heterochromatin/*genetics/metabolism/ultrastructure
MH  - Humans
MH  - Promoter Regions, Genetic/genetics
MH  - Repressor Proteins/genetics
MH  - Retinoblastoma Protein/*genetics/metabolism
MH  - Transcription Factors/*genetics/metabolism
MH  - Tumor Suppressor Proteins/*genetics/metabolism
EDAT- 2003/06/18 05:00
MHDA- 2003/07/24 05:00
CRDT- 2003/06/18 05:00
PHST- 2003/06/18 05:00 [pubmed]
PHST- 2003/07/24 05:00 [medline]
PHST- 2003/06/18 05:00 [entrez]
AID - S009286740300401X [pii]
AID - 10.1016/s0092-8674(03)00401-x [doi]
PST - ppublish
SO  - Cell. 2003 Jun 13;113(6):703-16. doi: 10.1016/s0092-8674(03)00401-x.