Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities
Open accessAbstract
Mdm4 is a critical inhibitor of the p53 tumor suppressor. Mdm4 null mice die early during embryogenesis due to increased p53 activity. In this study, we explore the role that Mdm4 plays in the intestinal epithelium by crossing mice carrying the Mdm4 floxed allele to mice with the Villin Cre transgene. Our data show that loss of Mdm4 (Mdm4intDelta) in this tissue resulted in viable animals with no obvious morphological abnormalities. However, these mutants displayed increased p53 levels and apoptosis exclusively in the proliferative compartment of the intestinal epithelium. This phenotype was completely rescued in a p53 null background. Notably, the observed compartmentalized apoptosis in proliferative intestinal epithelial cells was not due to restricted Mdm4 expression in this region. Thus, in this specific cellular context, p53 is negatively regulated by Mdm4 exclusively in highly proliferative cells.
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In smooth muscle cells, loss of Mdmx has no phenotype.
“However, in other cases, such as smooth muscle cells, loss of Mdmx has no phenotype.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [37]
In some tissues and cell types, such as the central nervous system and proliferative intestinal cells, there is a requirement for both Mdm2 and Mdmx.
“Clearly in some tissues and cell types [such as the central nervous system (CNS) and proliferative intestinal cells], there is a requirement for both Mdm2 and Mdmx.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [37]
Mdm2 and Mdmx contribute to p53 regulation to different extents in different tissues in vivo.
“Mdm2 and Mdmx seem to contribute to p53 regulation to different extents in different tissues in vivo (Table 1; [32–40]).”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [37]
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- Authors
- Valentin-Vega, Y. A., Box, N., Terzian, T., & Lozano, G.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- University of Colorado Denver (US)
- Corresponding author
- Lozano, Guillermina
- Venue
- Differentiation
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 77
- Issue
- 5
- Pages
- 442-449
- ISSN
- 0301-4681 (ISSN-L)
- PMC
- PMC4041067
- OpenAlex
- W2008316167
- Cited by
- 28
- References
- 37
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Differentiation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA47296, R01CA047296)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- MDM4, p53, intestinal epithelium, apoptosis, intestinal proliferation
- MeSH terms
- Animals, beta-Galactosidase, Bromodeoxyuridine, Crosses, Genetic, Intestinal Mucosa, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Proto-Oncogene Proteins, Tumor Suppressor Protein p53, Apoptosis, Mice, Knockout, Transgenes, Ubiquitin-Protein Ligases, Mice
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