A5031423419- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Gene Regulatory Network Analysis
- Fungal and yeast genetics research
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Single-cell and spatial transcriptomics
- Radiopharmaceutical Chemistry and Applications
- Cell death mechanisms and regulation
- Medical Imaging Techniques and Applications
- Gene expression and cancer classification
- Ubiquitin and proteasome pathways
- Bioinformatics and Genomic Networks
- Genetic factors in colorectal cancer
- Medical Imaging and Pathology Studies
- Liver physiology and pathology
- RNA Interference and Gene Delivery
- Breast Cancer Treatment Studies
- interferon and immune responses
- Molecular Biology Techniques and Applications
Centre National de la Recherche Scientifique
2002-2022
Université de Montpellier
2011-2022
Institut de Génétique Moléculaire de Montpellier
2008-2021
Centre National pour la Recherche Scientifique et Technique (CNRST)
2016
Canadian Nautical Research Society
2012
Scripps Research Institute
1991-2007
Centre de Recherche en Biologie cellulaire de Montpellier
1998-2007
Université Côte d'Azur
1995-1998
University of North Carolina at Chapel Hill
1994
University of California, San Diego
1992
G1 cyclins control the to S phase transition in budding yeast, Saccharomyces cerevisiae. Cyclin E was discovered course of a screen for human complementary DNAs that rescue deficiency cyclin function yeast. The amounts both protein and an associated kinase activity fluctuated periodically through cell cycle; were maximal late early phases. E-associated correlated with appearance complexes containing cyclin-dependent Cdk2. Thus, E-Cdk2 complex may constitute G1-S phase-specific regulatory kinase.
The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation retinoblastoma protein (pRb). We show that Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively aging cells, binds to and inactivates all cyclin E-Cdk2 whereas young cells only p21-free Cdk2 are active. Furthermore, senescent-cell-cycle occurs prior accumulation Cdk4-Cdk6 p16(Ink4a), suggesting...
Cyclin E is classified as a putative G1 cyclin on the basis of its cyclic pattern mRNA expression, with maximal levels being detected near G1/S boundary. We report here that found associated transcription factor E2F in temporally regulated fashion. known to be critical for expression some S phase-specific proteins and thought important series others. Antisera specific were raised used demonstrate an association between E2F. This E/E2F complex was seen variety human cell lines from various...
Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It widely used cancer histopathology but its functions remain unclear. Here, we show that controls heterochromatin organisation. Altering expression levels did not significantly affect cell proliferation vivo. mutant mice developed normally and cells lacking proliferated efficiently. Conversely, upregulation of differentiated tissues prevent cycle arrest. interactors included proteins involved nucleolar processes...
The cell proliferation antigen Ki-67 is widely used in cancer histopathology, but estimations of expression levels are inconsistent and understanding its regulation limited. Here we show that cell-cycle underlies variable all situations analyzed, including nontransformed human cells, normal mouse intestinal epithelia adenomas, lines with or without drug treatments, breast colon cancers. In was a late marker entry; mRNA oscillated highest G2 while protein increased throughout the cycle,...
Diurnal oscillations of gene expression controlled by the circadian clock and its connected feeding rhythm enable organisms to coordinate their physiologies with daily environmental cycles. While available techniques yielded crucial insights into regulation at transcriptional level, much less is known about temporally functions within nucleus protein level. Here, we quantified temporal nuclear accumulation proteins phosphoproteins from mouse liver SILAC proteomics. We identified around 5,000...
Cell cycle arrest in G1 response to ionizing radiation or senescence is believed be provoked by inactivation of cyclin-cyclin-dependent kinases (Cdks) the Cdk inhibitor p21Cip1/Waf1/Sdi1. We provide evidence that addition exerting negative control G1/S phase transition, p21 may play a role at onset mitosis. In nontransformed fibroblasts, transiently reaccumulates nucleus near G2/M-phase boundary, concomitant with cyclin B1 nuclear translocation, and associates fraction A-Cdk B1-Cdk...
Cyclin-dependent kinases (Cdks) previously have been shown to drive the major cell cycle transitions in eukaryotic organisms ranging from yeast humans. We report here identification of a 28-kDa protein, p28Ick (inhibitor cyclin-dependent kinase), that binds and inhibits kinase activity preformed Cdk/cyclin complexes human cells. p28 inhibitory fluctuates during with maximal levels G1 accumulates G1- G0-arrested These results suggest control G1/S transition may be influenced by family Cdk...
Senescent human diploid fibroblasts are unable to enter S phase in response mitogenic stimulation. One of the key deficiencies mitogen-stimulated senescent cells is their failure phosphorylate retinoblastoma protein, which acts as an inhibitor entry into its unphosphorylated form. Recent data suggest that cyclin-dependent kinases (Cdks) regulated by G1 cyclins (D type and E) responsible for primary phosphorylation protein prior G1/S boundary. Surprisingly, we found 10- 15-fold higher...
G2 arrest of cells suffering DNA damage in S phase is crucial to avoid their entry into mitosis, with the concomitant risks oncogenic transformation. According current model, signals elicited by prevent mitosis inhibiting both activation and nuclear import cyclin B1-Cdk1, a master mitotic regulator. We now show that normal human fibroblasts use additional mechanisms block B1-Cdk1. In these cells, exposure nonrepairable leads accumulation inactive B1-Cdk1 complexes. This retention, which...
Since the mid 1970s, cancer has been described as a process of Darwinian evolution, with somatic cellular selection and evolution being fundamental processes leading to malignancy its many manifestations (neoangiogenesis, evasion immune system, metastasis, resistance therapies). Historically, little attention placed on applications evolutionary biology understanding controlling neoplastic progression prevent therapeutic failures. This is now beginning change, there growing international...
Abstract Although cyclin-dependent kinase 2 (Cdk2) controls the G1/S transition and promotes DNA replication, it is dispensable for cell cycle progression due to redundancy with Cdk1. Yet Cdk2 also has non-redundant functions that can be revealed in certain genetic backgrounds was reported promote G2/M damage response checkpoint TP53 (p53)-deficient cancer cells. However, p53-proficient cells subjected damage, inactivated by CDK inhibitor p21. We therefore investigated whether differentially...
AbstractIrreversible G1 arrest in senescent human fibroblasts is mediated by two inhibitors of cyclin-dependent kinases (Cdks), p21Cip1/SDI1/WAF1 and p16Ink4A. To determine the physiological molecular events that specifically require p21, we studied senescence diploid expressing papillomavirus type 16 E6 oncogene, which confers low p21 levels via enhanced p53 degradation. We show late-passage cells, high Cdk activity drives cell cycle, but population expansion slowed down crisis-like events,...
ABSTRACT Senescence is an irreversible withdrawal from cell proliferation that can be initiated after DNA damage-induced cycle arrest in G2 phase to prevent genomic instability. onset requires p53 (also known as TP53) and retinoblastoma protein (RB, also RB1) family tumour suppressors, but how they are regulated convert a temporary into permanent one remains unknown. Here, we show previously unrecognised balance between the cyclin-dependent kinase (CDK) inhibitor p21 checkpoint Chk1 controls...