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Research ArticleThe Toll-Like Receptor/MyD88/XBP1 Signaling Axis Mediates Skeletal Muscle Wasting during Cancer CachexiaSkeletal muscle wasting causes both morbidity and mortality of cancer patients. Accumulating evidence suggests that the markers of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways are increased in skeletal muscle under multiple catabolic conditions, including cancer. However, the signaling mechanisms and the role of individual arms of the UPR in the regulation of skeletal muscle mass remain largely unknown...
Research ArticleFANCD2 Binding to H4K20me2 via a Methyl-Binding Domain Is Essential for Efficient DNA Cross-Link RepairFanconi anemia (FA) is an inherited disease characterized by bone marrow failure and increased cancer risk. FA is caused by mutation of any 1 of 22 genes, and the FA proteins function cooperatively to repair DNA interstrand cross-links (ICLs). A central step in the activation of the FA pathway is the monoubiquitination of the FANCD2 and FANCI proteins, which occurs within chromatin. How FANCD2 and FANCI are anchored to chromatin remains...
Research ArticleCell Cycle Kinase Polo Is Controlled by a Widespread 3′ Untranslated Region Regulatory Sequence in Drosophila melanogasterAlternative polyadenylation generates transcriptomic diversity, although the physiological impact and regulatory mechanisms involved are still poorly understood. The cell cycle kinase Polo is controlled by alternative polyadenylation in the 3′ untranslated region (3′UTR), with critical physiological consequences. Here, we characterized the molecular mechanisms required for polo alternative polyadenylation.
Research Article | SpotlightSelective Kinase Inhibition Shows That Bur1 (Cdk9) Phosphorylates the Rpb1 Linker In VivoCyclin-dependent kinases play multiple roles in RNA polymerase II transcription. Cdk7/Kin28, Cdk9/Bur1, and Cdk12/Ctk1 phosphorylate the polymerase and other factors to drive the dynamic exchange of initiation and elongation complex components over the transcription cycle. We engineered strains of the yeast Saccharomyces cerevisiae for rapid, specific inactivation of...
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The first nonsurgical cancer therapy was bacterial therapy introduced in 1891 to treat solid tumors. Because in many cases it was harmful and ineffective, and with the emergence of radiotherapy and chemotherapy, bacterial therapy was discontinued.