A5057443277- Cancer-related Molecular Pathways
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- CAR-T cell therapy research
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Telomeres, Telomerase, and Senescence
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Cancer-related gene regulation
- RNA Research and Splicing
- Toxin Mechanisms and Immunotoxins
- interferon and immune responses
- CRISPR and Genetic Engineering
- Ferroptosis and cancer prognosis
- Chromosomal and Genetic Variations
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- T-cell and Retrovirus Studies
- Fungal and yeast genetics research
Sorbonne Université
2012-2025
Institut Curie
2012-2025
Université Paris Sciences et Lettres
2016-2025
Centre National de la Recherche Scientifique
2012-2025
Université Paris 1 Panthéon-Sorbonne
2023-2024
Dynamique de l'information génétique : bases fondamentales et cancer
2012-2024
Ninewells Hospital
2024
Sorbonne University Abu Dhabi
2024
University of Dundee
2024
Université Paris Cité
2016-2017
In mammals, centromere definition involves the histone variant CENP-A (centromere protein A), deposited by its chaperone, HJURP (Holliday junction recognition protein). Alterations in this process impair chromosome segregation and genome stability, which are also compromised p53 inactivation cancer. Here we found that transcriptionally up-regulated p53-null human tumors. Using an established mouse embryonic fibroblast (MEF) model combining with E1A or HRas-V12 oncogene expression, reproduced...
Mutations in p53, although frequent human cancers, have not been implicated telomere-related syndromes.Here, we show that homozygous mutant mice expressing p53 D31 , a lacking the C-terminal domain, exhibit increased activity and suffer from aplastic anemia pulmonary fibrosis, hallmarks of syndromes caused by short telomeres.Indeed, D31/D31 had telomeres other phenotypic traits associated with telomere disease dyskeratosis congenita its severe variant Hoyeraal-Hreidarsson...
Abstract Germline mutations affecting telomere maintenance or DNA repair may, respectively, cause dyskeratosis congenita Fanconi anaemia, two clinically related bone marrow failure syndromes. Mice expressing p53 Δ31 , a mutant lacking the C terminus, model congenita. Accordingly, increased activity in Δ31/Δ31 fibroblasts correlated with decreased expression of 4 genes implicated Here we show that these cells exhibit mRNA levels for additional contributing to metabolism, but also,...
Missense “hotspot” mutations localized in six p53 codons account for 20% of TP53 human cancers. Hotspot mutants have lost the tumor suppressive functions wildtype protein, but whether and how they may gain additional promoting tumorigenesis remain controversial. Here we generated Trp53 Y217C , a mouse model hotspot mutant Y220C . DNA damage responses were Y217C/Y217C cells, fibroblasts exhibited increased chromosome instability compared to -/- cells. Furthermore, male mice died earlier than...
Dyskeratosis congenita is a cancer-prone inherited bone marrow failure syndrome caused by telomere dysfunction. A mouse model recently suggested that p53 regulates metabolism, but the clinical relevance of this finding remained uncertain. Here, germline missense mutation MDM4, negative regulator p53, was found in family with features suggestive dyskeratosis congenita, e.g., hypocellularity, short telomeres, tongue squamous cell carcinoma, and acute myeloid leukemia. Using model, we show...
p53 (encoded by Trp53) is a tumor suppressor, but mouse models have revealed that increased activity may cause bone marrow failure, likely through dimerization partner, RB-like, E2F4/E2F5 and MuvB (DREAM) complex-mediated gene repression. Here, we designed systematic approach to identify p53-DREAM pathway targets, the repression of which might contribute abnormal hematopoiesis. We used Gene Ontology analysis study transcriptomic changes associated with cell differentiation, then chromatin...
Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as germline mutation in one allele promotes retinoblastoma humans, but not mice. Here we show p53 transactivates Retinoblastoma-like 2 (Rbl2) to produce p130 murine, human, cells. We found intronic fuzzy tandem repeats containing perfect response elements be important for this regulation. next identified two other murine genes...
The Trp53 gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the alternatively spliced (AS) exon, thereby expressing canonical p53 protein but not with AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in +/+ Eμ-Myc males compared to ΔAS/ΔAS males, also and females. Pre-tumoral splenic cells from exhibited higher expression Ackr4, encoding an atypical chemokine...
The gene encoding p53, a major tumor suppressor protein, encodes several alternative isoforms of elusive biological significance. Here we show that mice lacking the Trp53 Alternatively Spliced (AS) exon, thereby expressing canonical p53 protein but not with AS C-terminus, have unexpectedly lost male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in +/+ Eμ-Myc males compared to ΔAS/ΔAS males, also and females. Pre-tumoral splenocytes from exhibited...
The Trp53 gene encodes several isoforms of elusive biological significance. Here we show that mice lacking the Alternatively Spliced (AS) exon, thereby expressing canonical p53 protein but not with AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in +/+ Eμ-Myc males compared to ΔAS/ΔAS males, also and females. Pre-tumoral splenic cells from exhibited higher expression Ackr4, encoding an atypical chemokine...
The Trp53 gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the alternatively spliced (AS) exon, thereby expressing canonical p53 protein but not with AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in +/+ Eμ-Myc males compared to ΔAS/ΔAS males, also and females. Pre-tumoral splenic cells from exhibited higher expression Ackr4, encoding an atypical chemokine...
Missense "hotspot" mutations localized in six p53 codons account for 20% of TP53 human cancers. Hotspot mutants have lost the tumor suppressive functions wildtype protein, but whether they may gain additional promoting tumorigenesis remains controversial. Here we generated Trp53 Y217C , a mouse model hotspot mutant Y220C . DNA damage responses were Y217C/Y217C cells. Surprisingly, intercrosses from +/Y217C heterozygotes yielded only one female nineteen males at weaning, skewed distribution...
Missense “hotspot” mutations localized in six p53 codons account for 20% of TP53 human cancers. Hotspot mutants have lost the tumor suppressive functions wildtype protein, but whether they may gain additional promoting tumorigenesis remains controversial. Here we generated Trp53 Y217C , a mouse model hotspot mutant Y220C . DNA damage responses were Y217C/Y217C cells. Surprisingly, intercrosses from +/Y217C heterozygotes yielded only one female nineteen males at weaning, skewed distribution...
Missense “hotspot” mutations localized in six p53 codons account for 20% of TP53 human cancers. Hotspot mutants have lost the tumor suppressive functions wildtype protein, but whether they may gain additional promoting tumorigenesis remains controversial. Here we generated Trp53 Y217C , a mouse model hotspot mutant Y220C . DNA damage responses were Y217C/Y217C cells. Surprisingly, intercrosses from +/Y217C heterozygotes yielded only one female nineteen males at weaning, skewed distribution...
Understanding the effect of an ever-growing number human variants detected by genome sequencing is a medical challenge. The yeast Saccharomyces cerevisiae model has held attention for its capacity to monitor functional impact missense mutations found in genes, including BRCA1 breast and ovarian cancer susceptibility gene. When expressed yeast, wild-type full-length protein forms single nuclear aggregate induces growth inhibition. Both events are modified pathogenic BRCA1. However, biological...
The clinical importance of tumor suppressor p53 makes it one the most studied transcription factors. A comparison mammalian transcriptional repertoires may help identify fundamental principles in genome evolution and better understand cancer processes. Here we summarize mechanisms underlying divergence repertoires, with an emphasis on rapid fuzzy tandem repeats containing response elements.
Abstract p53 is mainly known as a tumor suppressor, but mouse models revealed that increased activity may cause bone marrow failure, through mechanisms likely include gene repression mediated by the p53-DREAM pathway. Here we designed systematic approach to identify targets whose might contribute abnormal hematopoiesis. We used ontology analyze transcriptomic changes associated with cell differentiation and activation, then ChIP-seq data find promoters bound DREAM complex. next created...
Abstract The Trp53 gene encodes several isoforms of elusive biological significance. Here we show that mice lacking the Alternatively Spliced (AS) exon, thereby expressing canonical p53 protein but not with AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in +/+ Eμ-Myc males compared to ΔAS/ΔAS males, also and females. Pre-tumoral splenic cells from exhibited higher expression Ackr4, encoding an atypical...