We have previously shown that IKKs are aberrantly activated in colon cancer cells leading to SMRT phosphorylation and its release from the chromatin. We now show that IKKalpha phosphorylates the homologous N-CoR corepressor in serines 2345 and 2348 creating a functional 14-3-3 binding domain (RK(p)S(2348)KSP). Moreover, we have analyzed the subcellular localization of N-CoR in 43 colorectal cancer samples and we have found that aberrant cytoplasmic distribution of N-CoR is a general trait of these tumors.
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http://dx.doi.org/10.4161/cc.6.14.4429 | DOI Listing |
Biochim Biophys Acta Gen Subj
January 2025
Graduate School of Life Science, Hokkaido University, Sapporo 060-0812, Japan; Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Biomolecular condensates like U-bodies are specialized cellular structures formed through multivalent interactions among intrinsically disordered regions. U-bodies sequester small nuclear ribonucleoprotein complexes (snRNPs) in the cytoplasm, and their formation in mammalian cells depends on stress conditions. Because of their location adjacent to P-bodies, U-bodies have been considered potential sites for snRNP storage or turnover.
View Article and Find Full Text PDFPLoS Genet
January 2025
Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st St. SW, Rochester, Minnesota 55905, United States of America.
Motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy, involve loss of muscle control resulting from death of motor neurons. Although the exact pathogenesis of these syndromes remains elusive, many are caused by genetically inherited mutations. Thus, it is valuable to identify additional genes that can impact motor neuron survival and function.
View Article and Find Full Text PDFSci Adv
January 2025
Cellular Homeostasis and Recycling, Danish Cancer Institute, DK-2100 Copenhagen, Denmark.
Nutrient deprivation is a major trigger of autophagy, a conserved quality control and recycling process essential for cellular and tissue homeostasis. In a high-content image-based screen of the human ubiquitome, we here identify the E3 ligase Pellino 3 (PELI3) as a crucial regulator of starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with the ATG8 proteins through an LC3-interacting region (LIR).
View Article and Find Full Text PDFBackground: The interactions between virus and the host immune response are nuanced and intricate. The cytokine response arguably plays a central role in dictating the outcome of virus infection, balancing inflammation and healing, which is crucial to resolving infection without destructive immunopathologies.
Summary: Early innate immune responses are key to the generation of a beneficial or detrimental immune response.
Cell Rep
January 2025
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Pharmacology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS.
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