Publications by authors named "Bassem Shebl"
Proper codon/anticodon pairing within the ribosome necessitates linearity of the transcript. Any structures formed within a messenger RNA (mRNA) must be unwound before the respective codon is interpreted. Linearity, however, is not always the norm; some intricate structures within mRNA are able to exert unique ribosome/mRNA interactions to regulate translation.
View Article and Find Full Text PDFArticle Synopsis
- * This study introduces a novel PROTAC called StIP-TAC, which recruits E3 ligase to Protein Kinase A (PKA) using a hydrocarbon-stapled peptide, effectively promoting the degradation of PKA.
- * Treatment with StIP-TAC not only induced the degradation of PKA but also significantly reduced its activity by lowering phosphorylation of its substrates, suggesting that this approach can potentially target a wider range of proteins lacking suitable small molecule binding sites.
Article Synopsis
- Fibrolamellar hepatocellular carcinoma (FLC) is a rare type of liver cancer caused by a fusion of specific genes.
- Researchers found that in FLC, there is a higher ratio of active protein to regulatory proteins, which can cause the cancer to grow and spread.
- Changes in how a protein called PKA works and where it is located in the cell are more important for this cancer than the specific gene fusion itself.
Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis.
View Article and Find Full Text PDFFibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal liver cancer with no proven effective systemic therapy. Inhibition of the antiapoptotic protein BCL-XL was found to synergize with a variety of systemic therapies in vitro using cells dissociated from patient-derived xenografts (PDX) of FLC or cells dissociated directly from surgical patient resections. As BCL-XL is physiologically expressed in platelets, prior efforts to leverage this vulnerability in other cancers have been hampered by severe thrombocytopenia.
View Article and Find Full Text PDFHuman liver organoids for disease modeling of fibrolamellar carcinoma.
Stem Cell Reports
August 2022
Article Synopsis
- * Researchers created 21 organoid lines from tumor and non-tumor liver tissues, successfully mimicking the original cancer's characteristics for study purposes.
- * These patient-derived organoids serve as a promising model for drug testing and could significantly enhance our understanding of FLC and the development of future therapies.
To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin.
View Article and Find Full Text PDFPreparation of ribosomes for smFRET studies: A simplified approach.
Arch Biochem Biophys
August 2016
During the past decade, single-molecule studies of the ribosome have significantly advanced our understanding of protein synthesis. The broadest application of these methods has been towards the investigation of ribosome conformational dynamics using single-molecule Förster resonance energy transfer (smFRET). The recent advances in fluorescently labeled ribosomes and translation components have resulted in success of smFRET experiments.
View Article and Find Full Text PDFArticle Synopsis
- - The ribosome, a large macromolecular machine made of RNA and proteins, is crucial for protein synthesis, with key functional centers primarily composed of RNA, classifying it as a complex ribozyme.
- - It undergoes significant conformational changes during its activity, functioning also as a riboswitch, which has led to a deeper understanding of its mechanisms through recent advancements in single-molecule biophysics.
- - The text discusses the use of single-molecule Förster resonance energy transfer (FRET) in studying ribosome function, detailing experimental design from sample preparation to data analysis, applicable to other biological systems as well.