PMID- 21059851
OWN - NLM
STAT- MEDLINE
DCOM- 20110106
LR  - 20211020
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 191
IP  - 4
DP  - 2010 Nov 15
TI  - G1 arrest and differentiation can occur independently of Rb family function.
PG  - 809-25
LID - 10.1083/jcb.201003048 [doi]
AB  - The ability of progenitor cells to exit the cell cycle is essential for proper 
      embryonic development and homeostasis, but the mechanisms governing cell cycle 
      exit are still not fully understood. Here, we tested the requirement for the 
      retinoblastoma (Rb) protein and its family members p107 and p130 in G0/G1 arrest 
      and differentiation in mammalian cells. We found that Rb family triple knockout 
      (TKO) mouse embryos survive until days 9-11 of gestation. Strikingly, some TKO 
      cells, including in epithelial and neural lineages, are able to exit the cell 
      cycle in G0/G1 and differentiate in teratomas and in culture. This ability of TKO 
      cells to arrest in G0/G1 is associated with the repression of key E2F target 
      genes. Thus, G1 arrest is not always dependent on Rb family members, which 
      illustrates the robustness of cell cycle regulatory networks during 
      differentiation and allows for the identification of candidate pathways to 
      inhibit the expansion of cancer cells with mutations in the Rb pathway.
FAU - Wirt, Stacey E
AU  - Wirt SE
AD  - Department of Pediatrics, Stanford Medical School, Stanford, CA 94305, USA.
FAU - Adler, Adam S
AU  - Adler AS
FAU - Gebala, Veronique
AU  - Gebala V
FAU - Weimann, James M
AU  - Weimann JM
FAU - Schaffer, Bethany E
AU  - Schaffer BE
FAU - Saddic, Louis A
AU  - Saddic LA
FAU - Viatour, Patrick
AU  - Viatour P
FAU - Vogel, Hannes
AU  - Vogel H
FAU - Chang, Howard Y
AU  - Chang HY
FAU - Meissner, Alex
AU  - Meissner A
FAU - Sage, Julien
AU  - Sage J
LA  - eng
GR  - T32 CA009302/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101108
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Retinoblastoma-Like Protein p107)
RN  - 0 (Retinoblastoma-Like Protein p130)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Body Patterning/physiology
MH  - Cell Cycle/physiology
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Cell Differentiation/*physiology
MH  - Cells, Cultured
MH  - Embryo, Mammalian/anatomy & histology/physiology
MH  - Embryonic Stem Cells/cytology/physiology
MH  - Female
MH  - G1 Phase/*physiology
MH  - Gene Expression Profiling
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/cytology/physiology
MH  - Retinoblastoma Protein/genetics/*metabolism
MH  - Retinoblastoma-Like Protein p107/genetics/metabolism
MH  - Retinoblastoma-Like Protein p130/genetics/metabolism
MH  - Teratoma/metabolism/pathology
MH  - Transcription Factors/metabolism
PMC - PMC2983066
EDAT- 2010/11/10 06:00
MHDA- 2011/01/07 06:00
PMCR- 2011/05/15
CRDT- 2010/11/10 06:00
PHST- 2010/11/10 06:00 [entrez]
PHST- 2010/11/10 06:00 [pubmed]
PHST- 2011/01/07 06:00 [medline]
PHST- 2011/05/15 00:00 [pmc-release]
AID - jcb.201003048 [pii]
AID - 201003048 [pii]
AID - 10.1083/jcb.201003048 [doi]
PST - ppublish
SO  - J Cell Biol. 2010 Nov 15;191(4):809-25. doi: 10.1083/jcb.201003048. Epub 2010 Nov 
      8.