Mad2 Is a Critical Mediator of the Chromosome Instability Observed upon Rb and p53 Pathway Inhibition
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Multiple mechanisms have been proposed to explain how Rb and p53 tumor suppressor loss lead to chromosome instability (CIN). It was recently shown that Rb pathway inhibition causes overexpression of the mitotic checkpoint gene Mad2, but whether Mad2 overexpression is required to generate CIN in this context is unknown. Here, we show that CIN in cultured cells lacking Rb family proteins requires Mad2 upregulation and that this upregulation is also necessary for CIN and tumor progression in vivo. Mad2 is also repressed by p53 and its upregulation is required for CIN in a p53 mutant tumor model. These results demonstrate that Mad2 overexpression is a critical mediator of the CIN observed upon inactivation of two major tumor suppressor pathways.
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RB is important for p53-dependent downregulation of multiple genes.
“RB, too, is important for p53-dependent downregulation of multiple genes.100, 101, 102, 103”
From Census and evaluation of p53 target genes (2017) · cites this paper as [102]
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- Authors
- Schvartzman, J.-M., Duijf, P. H. G., Sotillo, R., Coker, C., & Benezra, R.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Benezra, Robert
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 19
- Issue
- 6
- Pages
- 701-714
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3120099
- OpenAlex
- W2021579554
- Cited by
- 181
- References
- 54
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 9 · 2020: 5 · 2019: 11 · 2018: 13 · 2017: 18 · 2016: 14 · 2015: 9 · 2014: 18 · 2013: 17 · 2012: 22
- FWCI
- 9.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 813 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion)
- Funders
- National Institutes of Health
- Susan G. Komen for the Cure
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- Mad2, chromosomal instability, retinoblastoma protein, p53, tumor suppressor pathways, spindle assembly checkpoint, tumor progression
- MeSH terms
- Animals, Calcium-Binding Proteins, Female, Humans, Mammary Neoplasms, Experimental, Mice, Inbred C57BL, Repressor Proteins, Signal Transduction, Tumor Suppressor Protein p53, Retinoblastoma Protein, Cell Cycle Proteins, Chromosomal Instability, HCT116 Cells, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21, Mice, Epithelial-Mesenchymal Transition, Mad2 Proteins
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