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Research Article | Spotlightp62-Dependent Phase Separation of Patient-Derived KEAP1 Mutations and NRF2Cancer-derived loss-of-function mutations in the KEAP1 tumor suppressor gene stabilize the NRF2 transcription factor, resulting in a prosurvival gene expression program that alters cellular metabolism and neutralizes oxidative stress. In a recent genotype-phenotype study, we classified 40% of KEAP1 mutations as ANCHOR mutants.
MinireviewWhen Long Noncoding Becomes Protein CodingRecent advancements in genetic and proteomic technologies have revealed that more of the genome encodes proteins than originally thought possible. Specifically, some putative long noncoding RNAs (lncRNAs) have been misannotated as noncoding. Numerous lncRNAs have been found to contain short open reading frames (sORFs) which have been overlooked because of their small size. Many of these sORFs encode small proteins or micropeptides with...
- MinireviewCentromere Biology: Transcription Goes on Stage
Accurate chromosome segregation is a fundamental process in cell biology. During mitosis, chromosomes are segregated into daughter cells through interactions between centromeres and microtubules in the mitotic spindle.
Research ArticleA Redox-Sensitive Thiol in Wis1 Modulates the Fission Yeast Mitogen-Activated Protein Kinase Response to H2O2 and Is the Target of a Small MoleculeOxidation of a highly conserved cysteine (Cys) residue located in the kinase activation loop of mitogen-activated protein kinase kinases (MAPKK) inactivates mammalian MKK6. This residue is conserved in the fission yeast Schizosaccharomyces pombe MAPKK Wis1, which belongs to the H2O2-responsive MAPK Sty1 pathway. Here, we show that H2O...
MinireviewSo Many Roads: the Multifaceted Regulation of Autophagy InductionAutophagy is an evolutionary conserved, degradative process from single-cell eukaryotes, such as Saccharomyces cerevisiae, to higher mammals, such as humans. The regulation of autophagy has been elucidated through the combined study of yeast, Caenorhabditis elegans, mice,...
MinireviewTranscriptional and Epigenomic Regulation of AdipogenesisUnderstanding adipogenesis, the process of adipocyte development, may provide new ways to treat obesity and related metabolic diseases. Adipogenesis is controlled by coordinated actions of lineage-determining transcription factors and epigenomic regulators.
Research Article | SpotlightNRF3-POMP-20S Proteasome Assembly Axis Promotes Cancer Development via Ubiquitin-Independent Proteolysis of p53 and Retinoblastoma ProteinProteasomes are essential protease complexes that maintain cellular homeostasis, and aberrant proteasomal activity supports cancer development. The regulatory mechanisms and biological function of the ubiquitin-26S proteasome have been studied extensively, while those of the ubiquitin-independent 20S proteasome system remain obscure. Here, we show that the cap ’n’ collar (CNC) family transcription factor NRF3 specifically enhances 20S...
Research ArticleOmomyc Reveals New Mechanisms To Inhibit the MYC OncogeneThe MYC oncogene is upregulated in human cancers by translocation, amplification, and mutation of cellular pathways that regulate Myc. Myc/Max heterodimers bind to E box sequences in the promoter regions of genes and activate transcription.
Research ArticleE3 Ubiquitin Ligase HRD1 Promotes Lung Tumorigenesis by Promoting Sirtuin 2 Ubiquitination and DegradationThe NAD-dependent histone deacetylase sirtuin 2 (SIRT2) plays critical roles in mitosis and cell cycle progression and recently was shown to suppress tumor growth and to be downregulated in several types of cancers. However, the underlying mechanism of SIRT2 downregulation remains unknown. In this study, using bioinformatics, gene expression profiling, protein overexpression approaches, and cell migration assays, we showed that E3...