A5026634249- Chronic Lymphocytic Leukemia Research
- Cancer Mechanisms and Therapy
- Advanced Breast Cancer Therapies
- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Immune Response and Inflammation
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Cytokine Signaling Pathways and Interactions
- Peptidase Inhibition and Analysis
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Hematopoietic Stem Cell Transplantation
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- interferon and immune responses
University of Veterinary Medicine Vienna
2022-2025
Abstract Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and replenish hematopoietic system. The cell-cycle kinase cyclin-dependent 6 (CDK6) regulates transcription, whereby it has both kinase-dependent kinase-independent functions. Herein, we describe complex role of CDK6, balancing quiescence, proliferation, self-renewal, differentiation in activated HSCs. Mouse HSCs expressing kinase-inactivated CDK6 show enhanced long-term repopulation homing, whereas...
Abstract Metabolic reprogramming and cell cycle deregulation are hallmarks of cancer cells. The kinase CDK6 has recently been implicated in a wide range hematopoietic malignancies. We here investigate the role regulation cellular metabolism BCR::ABL1+ leukemic Our study, using gene expression data ChIP-Seq analysis, highlights contribution activity oxidative phosphorylation. findings imply competition for promoter interaction with master regulator mitochondrial respiration, NRF-1. In line,...
Promoters of antimicrobial genes function as logic boards, integrating signals innate immune responses. One such set is stimulated by interferon (IFN) signaling, and the expression these [IFN-stimulated (ISGs)] can be further modulated cell stress–induced pathways. Here, we investigated global effect stress-induced p38 mitogen-activated protein kinase (MAPK) signaling on response macrophages to IFN. In stress that coincided with IFN exposure, MAPK-activated transcription factors CREB c-Jun,...
Cyclin-dependent kinase 6 (CDK6) represents a novel therapeutic target for the treatment of certain subtypes acute myeloid leukaemia (AML). CDK4/6 inhibitors have been widely studied in many cancer types and their effects may be limited by primary secondary resistance mechanisms. degraders, which eliminate kinase-dependent kinase-independent effects, suggested as an alternative option. We show that efficacy CDK6-specific protein degrader BSJ-03-123 varies among AML depends on low expression...
The vital cell cycle machinery is tightly regulated and alterations of its central signaling hubs are a hallmark cancer. activity CDK6 controlled by interaction with several partners including cyclins INK4 proteins, which have been shown to mainly bind the amino-terminal lobe. We analyzed impact CDK6's C-terminus on functions in leukemia model, revealing role promoting proliferation. C-terminally truncated Cdk6 (Cdk6 ΔC) shows reduced nuclear translocation therefore chromatin fails enhance...
Background: Cell-cycle progression is governed by regulatory proteins including cyclin-dependent kinases (CDKs), cyclins and CDK inhibitors. The INK4 family comprises p16INK4a, p15INK4b, p18INK4c p19INK4d which are CDK4/6 specific Different tumor types display deletion, mutation, or promoter hypermethylation of the resulting in enhanced activity. INK4a-ARF-INK4b locus encodes for p16INK4a p15INK4b suppressor protein p14ARF (p19ARF mouse) one most frequently mutated epigenetically silenced...