A5041997840- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- Telomeres, Telomerase, and Senescence
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Nuclear Structure and Function
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- Pancreatic and Hepatic Oncology Research
- interferon and immune responses
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Diet, Metabolism, and Disease
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
Centre Hospitalier de l’Université de Montréal
2019-2024
Université de Montréal
2016-2019
Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that stimulate the ERK pathway. Aberrantly high activation triggers oncogene-induced senescence, which halts tumor progression. Here we report low-grade pancreatic intraepithelial neoplasia displays very levels of phospho-ERK consistent with a senescence response. However, advanced lesions have circumvented barrier exhibit lower levels. Restoring hyperactivation PDAC using activated RAF leads to ERK-dependent growth arrest...
Several regulators of SUMOylation have been previously linked to senescence but most targets this modification in senescent cells remain unidentified. Using a two-step purification modified SUMO3, we profiled the SUMO proteome site-specific manner. We identified 25 sites on 23 proteins that were significantly regulated during senescence. Of note, these PML nuclear body (PML-NB) associated, which correlates with increased number and size PML-NBs observed cells. Interestingly, sole E2 enzyme,...
Mutants of lamin A cause diseases including the Hutchinson-Gilford progeria syndrome (HGPS) characterized by premature aging. Lamin undergoes a series processing reactions, farnesylation and proteolytic cleavage farnesylated C-terminal domain. The role is unknown but mutations that affect this reaction lead to progeria. Here we show interphase serine 22 phosphorylation endogenous mutant (progerin) defective in cells from HGPS patients. This defect can be mimicked expressing progerin human...
Senescence is a tumor suppressor program characterized by stable growth arrest while maintaining cell viability. Senescence-associated ribogenesis defects (SARD) have been shown to regulate senescence through the ability of ribosomal protein S14 (RPS14 or uS11) bind and inhibit cyclin-dependent kinase 4 (CDK4). Here we report another that binds inhibits CDK4 in senescent cells: L22 (RPL22 eL22). Enforcing expression RPL22/eL22 sufficient induce an RB p53-dependent cellular phenotype human...
We identify a senescence restriction point (SeRP) as critical event for cells to commit senescence. The SeRP integrates the intensity and duration of oncogenic stress, keeps memory previous stresses, combines signals acting on different pathways by modulating chromatin accessibility. Chromatin regions opened upon commitment are enriched in nucleolar-associated domains, which gene-poor repeated sequences. Once committed senescence, no longer depend initial stress signal exhibit characteristic...
The ubiquitin-associated protein 2–like (UBAP2L) gene remains poorly studied in human and mouse development. UBAP2L interacts with the Polycomb group B lymphoma Mo-MLV insertion region 1 homolog (BMI1) determines activity of hematopoietic stem cells vivo. Here we show that loss Ubap2l leads to disorganized respiratory epithelium mutant neonates, which die failure. We also overexpression epithelial-mesenchymal transition–like phenotype a non-small cell lung carcinoma (NSCLC) line. is...
Abstract This study aims to better understand the loss of tumor -uppression functions ERK in pancreatic cancer progression. Pancreatic is 4th leading cause death by Canada and USA with a 5-year survival rate below 7%. We have identified high level phosphorylation MAP kinase benign intraepithelial neoplasms (PanIN), followed reduction phospho-ERK levels ductal adenocarcinoma (PDAC) both human patient samples KRas-driven mouse models for cancer. Since PanINs are considered senescent lesions,...
Metabolic rewiring and redox balance play pivotal roles in cancer. Cellular senescence is a barrier for tumorigenesis circumvented cancer cells by poorly understood mechanisms. We report novel multi-enzymatic complex that reprograms NAD metabolism transferring reducing equivalents from NADH to NADP +. This hydride transfer (HTC) assembled Malate Dehydrogenase-1, Malic Enzyme-1 cytosolic Pyruvate Carboxylase. HTC enzymes are found phase-separated bodies the cytosol of can be vitro purified...