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RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition Universiteit Gent Vlaams Instituut voor Biotechnologie KU Leuven
High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or amplifications allowed identification of drivers for neuroblastoma development. Using this approach, combined with gene dosage impact on expression and survival, we identified ribonucleotide reductase subunit M2 (RRM2) as a candidate ...
MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR(+)/HER2(-) Metastatic Breast Cancer KU Leuven
Purpose: The phase II MONARCH 1 study was designed to evaluate the single-agent activity and adverse event (AE) profile of abemaciclib, a selective inhibitor of CDK4 and CDK6, in women with refractory hormone receptor-positive (HR(+)), HER2(-) metastatic breast cancer (MBC).Experimental Design: MONARCH 1 was a phase II single-arm open-label study. Women with HR(+)/HER2(-) MBC who had progressed on or after prior endocrine therapy and had 1 or 2 ...
CDK2 Regulates HIV-1 Transcription by Phosphorylation of CDK9 on Serine 90 KU Leuven
ABSTRACT:
Cdk1 and BRCA1 target gamma-tubulin to microtubule domains Universiteit Gent
CHEK1 and circCHEK1_246aa evoke chromosomal instability and induce bone lesion formation in multiple myeloma Vrije Universiteit Brussel
BACKGROUND: Multiple myeloma (MM) is still incurable and characterized by clonal expansion of plasma cells in the bone marrow (BM). Therefore, effective therapeutic interventions must target both myeloma cells and the BM niche.
METHODS: Cell proliferation, drug resistance, and chromosomal instability (CIN) induced by CHEK1 were confirmed by Giemsa staining, exon sequencing, immunofluorescence and xenograft model in vivo. Bone lesion ...
The Neural Cell Adhesion Molecules L1 and CHL1 Are Cleaved by BACE1 Protease in Vivo KU Leuven Universiteit Gent
The β-site amyloid precursor protein-cleaving enzyme BACE1 is a prime drug target for Alzheimer disease. However, the function and the physiological substrates of BACE1 remain largely unknown. In this work, we took a quantitative proteomic approach to analyze the secretome of primary neurons after acute BACE1 inhibition, and we identified several novel substrate candidates for BACE1. Many of these molecules are involved in neuronal network ...
Cdk1 orders mitotic events through coordination of a chromosome-associated phosphatase switch KU Leuven
RepoMan is a scaffold for signalling by mitotic phosphatases at the chromosomes. During (pro)metaphase, RepoMan-associated protein phosphatases PP1 and PP2A-B56 regulate the chromosome targeting of Aurora-B kinase and RepoMan, respectively. Here we show that this task division is critically dependent on the phosphorylation of RepoMan by protein kinase Cyclin-dependent kinase 1 (Cdk1), which reduces the binding of PP1 but facilitates the ...
CHD1 assumes a central role during follicle development KU Leuven
During Bombyx mori follicle development, fine-tuning of chorion gene expression is under the control of bidirectional promoters. In this work, we show that the silkmoth chromo-helicase/ATPase-DNA binding protein 1 (CHD1) ortholog is responsible for repositioning of nucleosomes on chorion promoters, where the factor binds specifically. Chorion genes, occupying a single chromosomal locus, rely on an almost identical set of cis elements for their ...