ArticlePloS one2011
Separase loss of function cooperates with the loss of p53 in the initiation and progression of T- and B-cell lymphoma, leukemia and aneuploidy in mice.
Article in PloS one, 2011. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Role of chromosomal cohesion and separation in aneuploidy and tumorigenesis.Cellular and molecular life sciences : CMLS · 2024Review
- Gene Expression Pattern ofCancers · 2023Article
- Let-7c-5p Restrains Cell Growth and Induces Apoptosis of Lung Adenocarcinoma Cells via Targeting ESPL1.Molecular biotechnology · 2022Article
- Mapping separase-mediated cleavage in situ.NAR genomics and bioinformatics · 2022Article
- Aneuploidy as a promoter and suppressor of malignant growth.Nature reviews. Cancer · 2021Review
- p53 Is Not Required for High CIN to Induce Tumor Suppression.Molecular cancer research : MCR · 2021Article
- Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants.Neurobiology of disease · 2020Article
- Role of chromosomal architecture in germinal center B cells and lymphomagenesis.Current opinion in hematology · 2019Review
- Local activation of mammalian separase in interphase promotes double-strand break repair and prevents oncogenic transformation.The EMBO journal · 2018Article
- Living in CIN: Mitotic Infidelity and Its Consequences for Tumor Promotion and Suppression.Developmental cell · 2016Review
- Article
- Positive and negative regulation of vertebrate separase by Cdk1-cyclin B1 may explain why securin is dispensable.The Journal of biological chemistry · 2015Article
- MMTV-Espl1 transgenic mice develop aneuploid, estrogen receptor alpha (ERα)-positive mammary adenocarcinomas.Oncogene · 2014Article
- A centrosomal route for cancer genome instability.Nature cell biology · 2014Article
- Chromosome missegregation rate predicts whether aneuploidy will promote or suppress tumors.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- The cancer biology of whole-chromosome instability.Oncogene · 2013Review
- 2n or not 2n: Aneuploidy, polyploidy and chromosomal instability in primary and tumor cells.Seminars in cell & developmental biology · 2013Article
- Cohesin complexes with a potential to link mammalian meiosis to cancer.Cell regeneration (London, England) · 2013Review
- Higher-order orchestration of hematopoiesis: is cohesin a new player?Experimental hematology · 2012Review
- Serum ESPL1 Can Be Used as a Biomarker for Patients With Hepatitis B Virus-Related Liver Cancer: A Chinese Case-Control Study.Technology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCohesin protease Separase plays a key role in faithful segregation of sister chromatids by cleaving the cohesin complex at the metaphase to anaphase transition. Homozygous deletion of ESPL1 gene that encodes Separase protein results in embryonic lethality in mice and Separase overexpression lead to aneuploidy and tumorigenesis. However, the effect of Separase haploinsufficiency has not been thoroughly investigated. METHODOLOGY/PRINCIPAL
findingsHere we examined the effect of ESPL1 heterozygosity using a hypomorphic mouse model that has reduced germline Separase activity. We report that while ESPL1 mutant (ESPL1 (+/hyp)) mice have a normal phenotype, in the absence of p53, these mice develop spontaneous T- and B-cell lymphomas, and leukemia with a significantly shortened latency as compared to p53 null mice. The ESPL1 hypomorphic, p53 heterozygous transgenic mice (ESPL1(+/hyp), p53(+/-)) also show a significantly reduced life span with an altered tumor spectrum of carcinomas and sarcomas compared to p53(+/-) mice alone. Furthermore, ESPL1(+/hyp), p53(-/-) mice display significantly higher levels of genetic instability and aneuploidy in normal cells, as indicated by the abnormal metaphase counts and SKY analysis of primary splenocytes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that reduced levels of Separase act synergistically with loss of p53 in the initiation and progression of B- and T- cell lymphomas, which is aided by increased chromosomal missegregation and accumulation of genomic instability. ESPL1(+/hyp), p53(-/-) mice provide a new animal model for mechanistic study of aggressive lymphoma and also for preclinical evaluation of new agents for its therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.