A5068103602- RNA modifications and cancer
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- PARP inhibition in cancer therapy
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Calcium signaling and nucleotide metabolism
- Advanced biosensing and bioanalysis techniques
- Acute Lymphoblastic Leukemia research
- Chromatin Remodeling and Cancer
- Genetics and Neurodevelopmental Disorders
- Diet, Metabolism, and Disease
- Polyamine Metabolism and Applications
- Cytomegalovirus and herpesvirus research
- interferon and immune responses
Danish Cancer Society
2021-2025
University Medical Center Groningen
2015-2021
University of Groningen
2015-2021
Cancer Genomics Centre
2014
Erasmus MC
2014
Highlights•The non-canonical PRC1.1 complex is critically important for human LSCs•Several members are overexpressed in primary AML•PRC1.1 can bind TSSs the absence of repressive H3K27me3 PRC2 mark•PRC1.1 targets actively transcribed genes involved metabolismSummaryPolycomb proteins classical regulators stem cell self-renewal and lineage commitment frequently deregulated cancer. Here, we find that complex, as identified by mass-spectrometry-based proteomics, leukemic cells. Downmodulation...
Impairment of translation can lead to collisions ribosomes, which constitute an activation platform for several ribosomal stress-surveillance pathways. Among these is the ribotoxic stress response (RSR), where sensing by MAP3K ZAKα leads p38 and JNK kinases. Despite insights, physiological ramifications impairment downstream RSR signaling remain elusive. Here, we show that stalling ribosomes sufficient activate ZAKα. In amino acid deprivation full nutrient starvation, impacts on ensuing...
Maintenance of epigenetic modifiers is utmost importance to preserve the epigenome and consequently appropriate cellular functioning. Here, we analyzed Polycomb group protein (PcG) complex integrity in response heat shock (HS). Upon HS, various Repressive Complex (PRC)1 PRC2 subunits, including CBX proteins, but also other chromatin regulators, are found accumulate nucleolus. In parallel, binding PRC1/2 target genes strongly reduced, coinciding with a dramatic loss H2AK119ub H3K27me3 marks....
Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent the ribosomal interactome, find deubiquitinase USP10 dissociates from ribosome transition to This release...
Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal DNA damage. Helix-distorting lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated binding CSB protein lesion-stalled RNA polymerase II. Using live cell imaging, we identify novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving...
In an attempt to unravel functionality of the non-canonical PRC1.1 Polycomb complex in human leukemogenesis, we show that USP7 and TRIM27 are integral components PRC1.1. interactome analyses is predominant co-precipitating with USP7. inhibition results disassembly loss chromatin binding, coinciding reduced H2AK119ub H3K27ac levels diminished gene transcription active PRC1.1-controlled loci, whereas marks also lost at PRC1 loci. reciprocally required for incorporation into PRC1.1, knockdown...
Nutrient deprivation is a major trigger of autophagy, conserved quality control and recycling process essential for cellular tissue homeostasis. In high-content image-based screen the human ubiquitome, we here identify E3 ligase Pellino 3 (PELI3) as crucial regulator starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with ATG8 proteins through an LC3-interacting region (LIR). This facilitates PELI3-mediated ubiquitination ULK1, driving...
Ribosomes are conserved macromolecular machines that responsible for protein synthesis in all cells. While our knowledge of ribosome biogenesis and function has increased significantly recent years, little is known about how ribosomes degraded under specific cellular conditions. We recently uncovered efficiently turned over by selective macroautophagy/autophagy during oncogene-induced senescence (OIS). By profiling the interactome human fibroblasts undergoing OIS, we discovered a key role...
ABSTRACT Acute myeloid leukemia (AML) is a highly heterogeneous disease in which genetic and epigenetic changes disturb regulatory mechanisms controlling stem cell fate maintenance. AML still remains difficult to treat, particular poor risk patients carrying TP53 mutations. Here, we identify the deubiquitinase USP7 as an integral member of non-canonical PRC1.1 show that targeting provides alternative therapeutic approach for AML. inhibitors effectively induced apoptosis (primary) cells, also...