Cell cycle-specific phase separation regulated by protein charge blockiness
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Description
Dynamic morphological changes of intracellular organelles are often regulated by protein phosphorylation or dephosphorylation1-6. Phosphorylation modulates stereospecific interactions among structured proteins, but how it controls molecular interactions among unstructured proteins and regulates their macroscopic behaviours remains unknown. Here we determined the cell cycle-specific behaviour of Ki-67, which localizes to the nucleoli during interphase and relocates to the chromosome periphery during mitosis. Mitotic hyperphosphorylation of disordered repeat domains of Ki-67 generates alternating charge blocks in these domains and increases their propensity for liquid–liquid phase separation (LLPS). A phosphomimetic sequence and the sequences with enhanced charge blockiness underwent strong LLPS in vitro and induced chromosome periphery formation in vivo. Conversely, mitotic hyperphosphorylation of NPM1 diminished a charge block and suppressed LLPS, resulting in nucleolar dissolution. Cell cycle-specific phase separation can be modulated via phosphorylation by enhancing or reducing the charge blockiness of disordered regions, rather than by attaching phosphate groups to specific sites.
Journal
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- Nature Cell Biology
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Nature Cell Biology 24 (5), 625-632, 2022-05-05
Springer Nature
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Details 詳細情報について
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- CRID
- 1050012932594502528
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- NII Book ID
- AA11338922
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- ISSN
- 14657392
- 14764679
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- HANDLE
- 2433/270023
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- KAKEN