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PMID: 11114893 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Ablation of the retinoblastoma gene family deregulates G(1) control causing immortalization and increased cell turnover under growth-restricting conditions.

Genes & development ·Vol. 14 ·No. 23 ·2000-12-01 ·Pages 3051-64

Dannenberg JH, van Rossum A, Schuijff L, te Riele H

Abstract

The retinoblastoma suppressor pRB belongs to the family of so-called pocket proteins, which also includes p107 and p130. These proteins may functionally overlap in cell cycle control and tumor suppression. We have generated an isogenic set of embryonic stem (ES) cell lines carrying single or compound loss-of-function mutations in the Rb gene family, including a cell line completely devoid of all three pocket proteins. None of the knockout combinations affected the growth characteristics of ES cells; however, concomitant ablation of all three pocket proteins strongly impaired their differentiation capacity. For the generated genotypes, primary mouse embryonic fibroblasts (MEFs) also were obtained. While inactivation of Rb alone did not alleviate the senescence response of MEFs, pRB/p107-deficient MEFs, after having adapted to in vitro culturing, continued to proliferate at modest rate. Additional ablation of p130 rendered MEFs completely insensitive to senescence-inducing signals and strongly increased their proliferation rate. Although triple-knockout MEFs retained anchorage dependence, they lacked proper G(1) control and showed increased cell turnover under growth-inhibiting conditions.

MeSH Terms
Animals Cell Adhesion Cell Differentiation/physiology Cell Division Cell Line G1 Phase Mice Mice, Inbred C57BL Mice, Knockout Mice, Nude Nuclear Proteins/genetics,metabolism,physiology Phosphoproteins/genetics,metabolism,physiology Proteins/metabolism Retinoblastoma Protein/genetics,metabolism,physiology Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Stem Cells/cytology Teratocarcinoma Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53/metabolism
Chemicals
Nuclear Proteins Phosphoproteins Proteins Rbl1 protein, mouse Rbl2 protein, mouse Retinoblastoma Protein Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Dannenberg J H
The Netherlands Cancer Institute, Division of Molecular Biology, 1066 CX Amsterdam, The Netherlands.
van Rossum A
Schuijff L
te Riele H
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.847700
Published
2000-12-01
Pages
3051-64
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317114
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.847700 PMC Full Text View journal details
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