Septins Regulate Actin Organization and Cell-Cycle Arrest through Nuclear Accumulation of NCK Mediated by SOCS7
Copyright policy )Septins Regulate Actin Organization and Cell-Cycle Arrest through Nuclear Accumulation of NCK Mediated by SOCS7
Mammalian septins are GTP-binding proteins the functions of which are not well understood. Knockdown of SEPT2, 6, and 7 causes stress fibers to disintegrate and cells to lose polarity. We now show that this phenotype is induced by nuclear accumulation of the adaptor protein NCK, as the effects can be reversed or induced by cytoplasmic or nuclear NCK, respectively. NCK is carried into the nucleus by SOCS7 (suppressor of cytokine signaling 7), which possesses nuclear import/export signals. SOCS7 interacts with septins and NCK through distinct domains. DNA damage induces actin and septin rearrangement and rapid nuclear accumulation of NCK and SOCS7. Moreover, NCK expression is essential for cell-cycle arrest. The septin-SOCS7-NCK axis intersects with the canonical DNA damage cascade downstream of ATM/ATR and is essential for p53 Ser15 phosphorylation. These data illuminate an unanticipated connection between septins, SOCS7, NCK signaling, and the DNA damage response.
- University of Virginia United States
Cytoplasm, Active Transport, Cell Nucleus, Cell Cycle Proteins, CELLCYCLE, Ataxia Telangiectasia Mutated Proteins, Mice, GTP-Binding Proteins, Animals, Humans, Hydroxyurea, Cell Shape, Adaptor Proteins, Signal Transducing, Cell Proliferation, Cell Nucleus, Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Cell Cycle, Actins, DNA-Binding Proteins, Cytoskeletal Proteins, SIGNALING, DNA Damage, HeLa Cells
Cytoplasm, Active Transport, Cell Nucleus, Cell Cycle Proteins, CELLCYCLE, Ataxia Telangiectasia Mutated Proteins, Mice, GTP-Binding Proteins, Animals, Humans, Hydroxyurea, Cell Shape, Adaptor Proteins, Signal Transducing, Cell Proliferation, Cell Nucleus, Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Cell Cycle, Actins, DNA-Binding Proteins, Cytoskeletal Proteins, SIGNALING, DNA Damage, HeLa Cells
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