ArticleOncogene2005
Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its ubiquitin-dependent proteasome degradation.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Silencing LINC01021 inhibits gastric cancer through upregulation of KISS1 expression by blocking CDK2-dependent phosphorylation of CDX2.Molecular therapy. Nucleic acids · 2021Article
- RHOA activity in expanding blastocysts is essential to regulate HIPPO-YAP signaling and to maintain the trophectoderm-specific gene expression program in a ROCK/actin filament-independent manner.Molecular human reproduction · 2019Article
- Fine-tuning and autoregulation of the intestinal determinant and tumor suppressor homeobox gene CDX2 by alternative splicing.Cell death and differentiation · 2017Article
- Icaritin enhances mESC self-renewal through upregulating core pluripotency transcription factors mediated by ERα.Scientific reports · 2017Article
- Extending the functions of the homeotic transcription factor Cdx2 in the digestive system through nontranscriptional activities.World journal of gastroenterology · 2015Review
- Article
- The cell cycle and pluripotency.The Biochemical journal · 2013Review
- Article
- Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.Developmental cell · 2010Article
- A novel domain mediates insulin-induced proteasomal degradation of insulin receptor substrate 1 (IRS-1).Molecular endocrinology (Baltimore, Md.) · 2010Article
- Hydrogen peroxide stimulates nuclear import of the POU homeodomain protein Oct-1 and its repressive effect on the expression of Cdx-2.BMC cell biology · 2010Article
- The intestine-specific transcription factor Cdx2 inhibits beta-catenin/TCF transcriptional activity by disrupting the beta-catenin-TCF protein complex.Carcinogenesis · 2010Article
- Cdx genes, inflammation, and the pathogenesis of intestinal metaplasia.Progress in molecular biology and translational science · 2010Review
- Down-regulation of Cdx2 in colorectal carcinoma cells by the Raf-MEK-ERK 1/2 pathway.Cellular signalling · 2009Article
- Trophoblast stem cells: models for investigating trophectoderm differentiation and placental development.Endocrine reviews · 2009Review
- Article
- Different effects of the Cdx1 and Cdx2 homeobox genes in a murine model of intestinal inflammation.Gut · 2007Article
- The microenvironment controls CDX2 homeobox gene expression in colorectal cancer cells.The American journal of pathology · 2007Article
- Functional interaction between the homeoprotein CDX1 and the transcriptional machinery containing the TATA-binding protein.Nucleic acids research · 2007Article
- Crosstalk between the cell cycle regulator Cdk2 and the Cdx2 tumor suppressor at the proliferation-differentiation interface.Oncogene · 2005Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Caudal-related homeodomain transcription factor Cdx2 plays a key role in intestinal cell fate determination. Reduction of Cdx2 expression is a feature of many human colon carcinomas and inactivation of one cdx2 allele facilitates the development of invasive adenocarcinoma in the murine colon. Here, we investigated the post-translational regulation of Cdx2. We showed that various forms of Cdx2 coexist in the intestine and colon cancer cell lines, some of them being phosphorylated forms. We found that cyclin-dependent kinase 2 phosphorylated Cdx2 in vitro and in vivo. Using site-specific mutagenesis, we identified serine 281 as a new key residue for Cdx2 phosphorylation. Intriguingly, serine 281 belongs to a conserved motif of four evenly spaced serines (the 4S motif) similar to the one controlling beta-catenin degradation by the proteasome pathway. A nonphosphorylated mutant Cdx2 lacking the 4S motif (4S>A) exhibited reduced polyubiquitination upon proteasome inhibition and increased stability compared to wild-type Cdx2. In addition, we found that this mutant was less efficient to suppress colony formation than wild-type Cdx2. Thus, our data highlight a novel post-translational mechanism controlling Cdx2 degradation via phosphorylation and polyubiquitination, which may be of importance for intestinal development and cancer.
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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.