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c-MYC and the SWI/SNF chromatin remodeling complex act as master regulators of transcription, and play a key role in human cancer. Although they are known to interact, the molecular details of their interaction are lacking. We have determined the structure of the RPT1 region of the INI1/hSNF5/BAF47/SMARCB1 subunit of the SWI/SNF complex that acts as a c-MYC-binding domain, and have localized the interaction regions on both INI1 and on the c-MYC:MAX heterodimer. c-MYC interacts with a highly conserved groove on INI1, while INI1 binds to the c-MYC helix-loop-helix region. The binding site overlaps with the c-MYC DNA-binding region, and we show that binding of INI1 and E-box DNA to c-MYC:MAX are mutually exclusive.
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http://dx.doi.org/10.1111/febs.14660 | DOI Listing |
Nat Prod Bioprospect
September 2025
College of Pharmaceutical Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnostics of Education Ministry of China, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei University, Baoding, 071002, People's Republic of China.
Five new heterodimers, chalasoergodimers A-E (1-5), and three known heterodimers (6-8), along with four chaetoglobosin monomers (9-12), were isolated from a marine-derived Chaetomium sp. fungus. The structures of new compounds 1-5 were elucidated by HRESIMS, NMR, chemical calculated C NMR and ECD methods.
View Article and Find Full Text PDFNat Commun
September 2025
Centre for Genomics and Oncological Research (GENYO), Avenue de la Ilustración 114, 18016, Granada, Spain.
Circadian oscillations of gene transcripts rely on a negative feedback loop executed by the activating BMAL1-CLOCK heterodimer and its negative regulators PER and CRY. Although circadian rhythms and CLOCK protein are mostly absent during embryogenesis, the lack of BMAL1 during prenatal development causes an early aging phenotype during adulthood, suggesting that BMAL1 performs an unknown non-circadian function during organism development that is fundamental for healthy adult life. Here, we show that BMAL1 interacts with TRIM28 and facilitates H3K9me3-mediated repression of transposable elements in naïve pluripotent cells, and that the loss of BMAL1 function induces a widespread transcriptional activation of MERVL elements, 3D genome reorganization and the acquisition of totipotency-associated molecular and cellular features.
View Article and Find Full Text PDFMol Biol Cell
September 2025
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
During embryonic development, neural crest-derived melanoblasts, which are precursors of pigment-producing melanocytes, disperse throughout the skin by long-range cell migration that requires adhesion to the ECM. Members of the integrin family of cell-ECM adhesion receptors are thought to contribute to melanocyte migration . However, due to the functional redundancy between different integrin heterodimers, the precise role of integrins in melanoblast migration, as well as the mechanisms that regulate them in this process, especially in contexts, remain poorly understood.
View Article and Find Full Text PDFElife
September 2025
Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali, India.
The UFD-1 (ubiquitin fusion degradation 1)-NPL-4 (nuclear protein localization homolog 4) heterodimer is involved in extracting ubiquitinated proteins from several plasma membrane locations, including the endoplasmic reticulum. This heterodimer complex helps in the degradation of ubiquitinated proteins via the proteasome with the help of the AAA+ATPase CDC-48. While the ubiquitin-proteasome system is known to have important roles in maintaining innate immune responses, the role of the UFD-1-NPL-4 complex in regulating immunity remains elusive.
View Article and Find Full Text PDFRSC Med Chem
August 2025
Department of Chemistry and Biochemistry, Baylor University, One Bear Place #97348, Waco, TX 76798-7348, United States of America.
A strategy for targeting tumor-associated hypoxia utilizes reductase enzyme-mediated cleavage to convert biologically inert prodrugs to their corresponding biologically active parent therapeutic agents selectively in areas of pronounced hypoxia. Small-molecule inhibitors of tubulin polymerization represent unique therapeutic agents for this approach, with the most promising functioning as both antiproliferative agents (cytotoxins) and as vascular disrupting agents (VDAs). VDAs selectively and effectively disrupt tumor-associated microvessels, which are typically fragile and chaotic in nature.
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