ArticleThe EMBO journal2011
RB regulates pancreas development by stabilizing Pdx1.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- CDK4-E2F3 signals enhance oxidative skeletal muscle fiber numbers and function to affect myogenesis and metabolism.The Journal of clinical investigation · 2023Article
- TGF-β Signaling in Pancreatic Islet β Cell Development and Function.Endocrinology · 2021Review
- Loss of Cyclin-dependent Kinase 2 in the Pancreas Links Primary β-Cell Dysfunction to Progressive Depletion of β-Cell Mass and Diabetes.The Journal of biological chemistry · 2017Article
- Transcriptional control of stem cell fate by E2Fs and pocket proteins.Frontiers in genetics · 2015Review
- Molecular ties between the cell cycle and differentiation in embryonic stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Mangiferin facilitates islet regeneration and β-cell proliferation through upregulation of cell cycle and β-cell regeneration regulators.International journal of molecular sciences · 2014Article
- Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: a novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin.Frontiers in physiology · 2014Review
- Article
- pRb controls estrogen receptor alpha protein stability and activity.Oncotarget · 2013Article
- The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the anti-apoptotic function of BAG-1 protein in colorectal tumour cells.Cell death & disease · 2012Article
- Angiotensin II regulates activation of Bim via Rb/E2F1 during apoptosis: involvement of interaction between AMPKβ1/2 and Cdk4.American journal of physiology. Lung cellular and molecular physiology · 2012Article
- A network of genes antagonistic to the LIN-35 retinoblastoma protein of Caenorhabditis elegans.Genetics · 2012Article
- The RB family is required for the self-renewal and survival of human embryonic stem cells.Nature communications · 2012Article
- Pdx1 is post-translationally modified in vivo and serine 61 is the principal site of phosphorylation.PloS one · 2012Article
- Newly identified aspects of tumor suppression by RB.Disease models & mechanisms · 2011Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
RB is a key substrate of Cdks and an important regulator of the mammalian cell cycle. RB either represses E2Fs that promote cell proliferation or enhances the activity of cell-specific factors that promote differentiation, although the mechanism that facilitates this dual interaction is unclear. Here, we demonstrate that RB associates with and stabilizes pancreatic duodenal homeobox-1 (Pdx-1) that is essential for embryonic pancreas development and adult β-cell function. Interestingly, Pdx-1 utilizes a conserved RB-interaction motif (RIM) that is also present in E2Fs. Point mutations within the RIM reduce RB-Pdx-1 complex formation, destabilize Pdx-1 and promote its proteasomal degradation. Glucose regulates RB and Pdx-1 levels, RB/Pdx-1 complex formation and Pdx-1 degradation. RB occupies the promoters of β-cell-specific genes, and knockdown of RB results in reduced expression of Pdx-1 and its target genes. Further, RB-deficiency in vivo results in reduced pancreas size due to decreased proliferation of Pdx-1(+) pancreatic progenitors, increased apoptosis and aberrant expression of regulators of pancreatic development. These results demonstrate an unanticipated regulatory mechanism for pancreatic development and β-cell function, which involves RB-mediated stabilization of the pancreas-specific transcription factor Pdx-1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.