Publications by authors named "Karen Stefanisko"
Article Synopsis
- The N-terminal domain of STAT3 is a potential target for cancer therapy and immune response modulation, but it's hard to reach with therapeutic antibodies since STAT3 is found in different cell compartments.
- This domain is considered "non-druggable" due to its surface structure lacking deep pockets for binding.
- The study used advanced virtual screening methods on massive compound libraries to identify potential inhibitors, indicating that broader chemical libraries can aid in creating drugs for challenging intracellular targets.
Article Synopsis
- Aerosol delivery of host directed therapies (HDTs) reduced the bacterial load of Mycobacterium tuberculosis in infected mice, showing significant bactericidal effects compared to control groups.* -
- Treatment with specific peptide inhibitors (ST3-H2A2 and IL10R1-7) enhanced the mice's bactericidal capacity, as indicated by increased activity of key enzymes and altered enzyme levels related to immune response.* -
- This study suggests that even without antibiotics, targeting the IL-10-STAT3 pathway could effectively lower bacterial levels in the lungs and influence important cellular processes like apoptosis and autophagy.*
Multiple genes in Mycobacterium tuberculosis (Mtb) are regulated by copper including socAB (small orf induced by copper A and B), which is induced by copper and repressed by RicR (regulated in copper repressor). socA and socB encode hypothetical proteins of 61 and 54 amino acids, respectively. Here, we use biophysical and computational methods to evaluate the SocB structure.
View Article and Find Full Text PDFArticle Synopsis
- Ras proteins activate effectors like Raf to transmit signals from receptors, but Raf needs to dimerize to be activated.
- The study shows that K-Ras4B, a cancer-related variant, forms stable homodimers with two main interfaces that influence its interaction with effectors.
- One interface inhibits effector binding while the other may enhance Raf activation, suggesting that targeting the dimerization could be a strategy for cancer treatment.
Article Synopsis
- Developed a new method to measure protein binding affinity using microscale thermophoresis (MST) without needing purified proteins, making it quicker and less costly.
- The protocol involves overexpressing a GFP-fused protein and lysing cells under gentle conditions, allowing for easier testing of interactions.
- Successfully applied this method to determine the binding affinity of the transcription factor STAT3-GFP to various DNA sequences, which could open new avenues for studying diverse protein interactions.
p205 is a member of the interferon-inducible p200 family of proteins that regulate cell proliferation. Over-expression of p205 inhibits cell growth, although its mechanism of action is currently unknown. Therefore, we evaluated the effect of p205 on the p53 and Rb-dependent pathways of cell cycle regulation.
View Article and Find Full Text PDFTo understand long terminal repeat (LTR)-retrotransposon copy number dynamics, Ty1 elements were reintroduced into a "Ty-less" Saccharomyces strain where elements had been lost by LTR-LTR recombination. Repopulated strains exhibited alterations in chromosome size that were associated with Ty1 insertions, but did not become genetically isolated. The rates of element gain and loss under genetic and environmental conditions known to affect Ty1 retrotransposition were determined using genetically tagged reference elements.
View Article and Find Full Text PDFBecause Ty elements transpose through an RNA intermediate, element accumulation through retrotransposition must be regulated or offset by element loss to avoid uncontrolled genome expansion. Here we examine the fate of Ty sequences in Saccharomyces strain 337, a strain that is reported to lack Ty1 and Ty2 elements, but contains remnant solo long terminal repeats (LTRs). Although strain 337 was initially classified as Saccharomyces cerevisiae, our work indicates that this strain is more closely related to S.
View Article and Find Full Text PDF