- Cellular transport and secretion
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Bacterial Genetics and Biotechnology
- Evolution and Genetic Dynamics
- Calcium signaling and nucleotide metabolism
- NF-κB Signaling Pathways
- Lipid Membrane Structure and Behavior
- Wnt/β-catenin signaling in development and cancer
- Retinal Development and Disorders
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- Reproductive System and Pregnancy
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Histone Deacetylase Inhibitors Research
- Biochemical and Structural Characterization
- interferon and immune responses
- Adenosine and Purinergic Signaling
- Endometriosis Research and Treatment
- Endometrial and Cervical Cancer Treatments
- DNA and Nucleic Acid Chemistry
Medical University of Warsaw
2021
International Institute of Molecular and Cell Biology
2007-2020
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
2005-2009
Because signaling mediated by the transcription factor nuclear κB (NF-κB) is initiated ligands and receptors that can undergo internalization, we investigated how endocytic trafficking regulated this key physiological pathway. We depleted all of ESCRT (endosomal sorting complexes required for transport) subunits, which mediate receptor degradation, found components Tsg101, Vps28, UBAP1, CHMP4B were essential to restrict constitutive NF-κB in human embryonic kidney 293 cells. In absence...
Summary Escherichia coli DNA polymerase III holoenzyme (HE) is the main replicase responsible for replication of bacterial chromosome. E. contains four additional polymerases, and it a relevant question whether these might also contribute to chromosomal its fidelity. Here, we have investigated role II (Pol II) ( polB gene product). Mismatch repair‐defective strains containing polBex1 allele – encoding polymerase‐proficient but exonucleolytically defective Pol displayed mutator activity...
We investigated the mutator effect resulting from overproduction of Escherichia coli DNA polymerase IV. Using lac mutational targets in two possible orientations on chromosome, we observed preferential mutagenesis during lagging strand synthesis. The activity likely results extension mismatches produced by III holoenzyme.
We have investigated the possible role of Escherichia coli DNA polymerase (Pol) I in chromosomal replication fidelity. This was done by substituting polA gene polAexo variant containing an inactivated 3'-->5' exonuclease, which serves as a proofreader for this enzyme's misinsertion errors. Using strain, activities Pol during might be detectable increases bacterial mutation rate. series defined lacZ reversion alleles two orientations on chromosome markers mutagenesis, 1.5- to 4-fold mutant...
ABSTRACT Constitutive expression of the SOS regulon in Escherichia coli recA730 strains leads to a mutator phenotype (SOS mutator) that is dependent on DNA polymerase V ( umuDC gene product). Here we show significant fraction this effect also requires IV dinB
Multifunctional adaptor protein APPL1 [adaptor containing PH (pleckstrin homology) domain, PTB (phosphotyrosine binding) domain and leucine zipper motif] belongs to a growing group of endocytic proteins which actively participate in various stages signalling pathways. Owing its interaction with the small GTPase Rab5, localizes predominantly subpopulation early endosomes but is also capable nucleocytoplasmic shuttling. Among binding partners, was reported associate nuclear co-repressor...
Abstract Background Lymphotoxin β receptor (LTβR) plays important roles in the development of immune system and response. At cellular level, ligand-bound LTβR activates pro-inflammatory NF-κB pathway but detailed mechanisms regulating its signaling remain unknown. Understanding them is high importance since ligands are promising therapeutic targets. Here, we studied consequences perturbed cholesterol content on LTβR-induced signaling. Methods To modulate availability and/or level lung...
Endometriosis is an inflammatory condition manifested by the presence of endometrial-like tissue outside uterine cavity. The most common clinical presentations endometriosis are dysmenorrhea, infertility, and severe pelvic pain. Few hypotheses attempt to explain pathogenesis endometriosis; however, none theories have been fully confirmed or considered universal. We examined somatic mutations in eutopic endometrium samples, deep endometriotic nodules peripheral blood from 13 women with...
Some endocytic proteins have recently been shown to play a role in tumorigenesis. In this study, we demonstrate that APPL2, an adapter protein with known functions, is upregulated 40% cases of glioblastoma multiforme, the most common and aggressive cancer central nervous system. The silencing APPL2 expression by small interfering RNAs (siRNAs) glioma cells markedly reduces cell survival under conditions low growth factor availability enhances apoptosis (measured executor caspase activity)....
Cytokine receptors, such as tumor necrosis factor receptor I (TNFRI, also known TNFRSF1A) and lymphotoxin β (LTβR), activate inflammatory nuclear (NF)-κB signaling upon stimulation. We have previously demonstrated that depletion of ESCRT components leads to endosomal accumulation TNFRI LTβR, their ligand-independent NF-κB. Here, we studied whether other perturbations the endolysosomal system could trigger intracellular ligand-free LTβR. While CORVET had no effect, knockdown Rab7a or HOPS...
Abstract Background Lymphotoxin β receptor (LTβR) is a member of tumor necrosis factor (TNFR) superfamily which regulates the immune response. At cellular level, upon ligand binding, activates pro-inflammatory NF-κB and AP-1 pathways. Yet, intracellular distribution LTβR, routes its endocytosis their connection to signaling activation are not characterized. Here, we investigated contribution LTβR internalization potential. Methods Intracellular localization in unstimulated stimulated cells...
APPL1 is a multifunctional endocytic adaptor which acts at different steps of various signaling pathways. Here we report that interacts with Dvl2, protein known to activate the canonical and non-canonical Wnt synergizes Dvl2 potentiates transcription driven by AP-1 factors, specifically c-Jun, in signaling. This function requires its endosomal recruitment. Overproduction increases Dvl2-mediated expression target gene encoding metalloproteinase 1 (MMP1) JNK-dependent manner. Collectively,...
Abstract Recent discoveries have suggested that some endocytic proteins are involved in multiple steps of cellular signaling, which starts from endocytosis activated receptors and is further transmitted the cytoplasm to nucleus. Two homologous adaptor APPL1 APPL2 seem constitute good examples such proteins, both (by interacting with small GTPase Rab5) signaling. They able translocate nucleus may participate regulation chromatin modification, raising a possibility their involvement control...