ArticleMolecular and cellular biology2002
The retinoblastoma protein binds the promoter of the survival gene bcl-2 and regulates its transcription in epithelial cells through transcription factor AP-2.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 62 citations in OpenAlex.
- Review
- Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views.Journal of translational medicine · 2023Review
- The atypical mitogen-activated protein kinase ERK3 is essential for establishment of epithelial architecture.The Journal of biological chemistry · 2018Article
- CHIP buffers heterogeneous Bcl-2 expression levels to prevent augmentation of anticancer drug-resistant cell population.Oncogene · 2015Article
- Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death.Carcinogenesis · 2015Review
- Expression of integrin alpha 10 is transcriptionally activated by pRb in mouse osteoblasts and is downregulated in multiple solid tumors.Cell death & disease · 2013Article
- Urokinase-type plasminogen activator receptor (uPAR)-mediated regulation of WNT/β-catenin signaling is enhanced in irradiated medulloblastoma cells.The Journal of biological chemistry · 2012Article
- Article
- Genome-wide analysis of transcription factor E2F1 mutant proteins reveals that N- and C-terminal protein interaction domains do not participate in targeting E2F1 to the human genome.The Journal of biological chemistry · 2011Article
- BCL-2 is a downstream target of ATF5 that mediates the prosurvival function of ATF5 in a cell type-dependent manner.The Journal of biological chemistry · 2011Article
- Two regions within the proximal steroidogenic factor 1 promoter drive somatic cell-specific activity in developing gonads of the female mouse.Biology of reproduction · 2011Article
- AP2 transcription factor induces apoptosis in retinoblastoma cells.Genes, chromosomes & cancer · 2010Article
- Investigation of the miR16-1 (C > T) + 7 Substitution in Seven Different Types of Cancer from Three Ethnic Groups.Journal of oncology · 2009Article
- Mutations in the SOD2 promoter reveal a molecular basis for an activating protein 2-dependent dysregulation of manganese superoxide dismutase expression in cancer cells.Molecular cancer research : MCR · 2008Article
- Transcription profiling of lung adenocarcinomas of c-myc-transgenic mice: identification of the c-myc regulatory gene network.BMC systems biology · 2008Article
- Cell autonomous roles for AP-2alpha in lens vesicle separation and maintenance of the lens epithelial cell phenotype.Developmental dynamics : an official publication of the American Association of Anatomists · 2008Article
- The immunoglobulin heavy-chain gene 3' enhancers deregulate bcl-2 promoter usage in t(14;18) lymphoma cells.Oncogene · 2007Article
- Intestinal mucositis: the role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2006Review
- Requirement of clathrin heavy chain for p53-mediated transcription.Genes & development · 2006Article
- GAS41 interacts with transcription factor AP-2beta and stimulates AP-2beta-mediated transactivation.Nucleic acids research · 2006Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The retinoblastoma (RB) gene product has been shown to restrict cell proliferation, promote cell differentiation, and inhibit apoptosis. Loss of RB function can induce both p53-dependent apoptosis and p53-independent apoptosis; little is known about the mechanisms of RB-regulated p53-independent apoptosis. Here we show that RB specifically activates transcription of the survival gene bcl-2 in epithelial cells but not in NIH 3T3 mesenchymal cells. This transcriptional activity is mediated by the transcription factor AP-2. By monitoring protein-DNA interactions in living cells using formaldehyde cross-linking and chromatin immunoprecipitation, we show that endogenous RB and AP-2 both bind to the same bcl-2 promoter sequence. In addition, we demonstrate that RB and AP-2 also bind to the E-cadherin gene promoter in vivo, consistent with regulation of this promoter by both AP-2 and RB in epithelial cells. This study provides evidence that RB activates bcl-2 and E-cadherin by binding directly to the respective promoter sequences and not indirectly by repressing an inhibitor. This recruitment is mediated by a transcription factor, in this case AP-2. For the first time, our results suggest a direct molecular mechanism by which RB might inhibit apoptosis independently of p53. The results are discussed in a context where RB and Bcl-2 contribute under nonpathological conditions to the maintenance of cell viability in association with a differentiated phenotype, contributing to the tumor suppressor function of RB and playing important roles in normal development.
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