Phasing in on the cell cycle - PubMed (original) (raw)

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Phasing in on the cell cycle

Steven Boeynaems et al. Cell Div. 2018.

Abstract

Just like all matter, proteins can also switch between gas, liquid and solid phases. Protein phase transition has claimed the spotlight in recent years as a novel way of how cells compartmentalize and regulate biochemical reactions. Moreover, this discovery has provided a new framework for the study of membrane-less organelle biogenesis and protein aggregation in neurodegenerative disorders. We now argue that this framework could be useful in the study of cell cycle regulation and cancer. Based on our work on phase transitions of arginine-rich proteins in neurodegeneration, via combining mass spectroscopy with bioinformatics analyses, we found that also numerous proteins involved in the regulation of the cell cycle can undergo protein phase separation. Indeed, several proteins whose function affects the cell cycle or are associated with cancer, have been recently found to phase separate from the test tube to cells. Investigating the role of this process for cell cycle proteins and understanding its molecular underpinnings will provide pivotal insights into the biology of cell cycle progression and cancer.

Keywords: Cancer; Centrosome; Nucleolus; Oncogenic fusion; Protein aggregation; Protein phase separation; Stress granules.

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Figures

Fig. 1

Fig. 1

Identification of the phase separating proteome. Cleared cell lysate was incubated with poly-PR peptide to induce phase separation of cellular proteins. Phase separated proteins were precipitated by mild centrifugation and subjected to mass spectrometry. Identified proteins included stress granule factors and other membrane-less organelle components, but surprisingly as well proteins annotated as implicated in the regulation of the cell cycle

Fig. 2

Fig. 2

Proteins regulating or affecting the cell cycle are involved in cellular phase separations. a Overview of different membraneless organelles (orange). The fold enrichment of cell cycle proteins (GO:0000278) is shown for each organelle for which the protein content was available. T cell signaling (GO:0050852) [40], stress granule [11], nuclear speckle (GO:0016607), RNP granule (GO:0035770), PML body [73], P body (GO:0000932), nuclear pore (GO:0005643) [74], nucleolus [75], centrosome (GO:0005813) [76]. APC granules and purinosomes were positive for cell cycle proteins APC [77] and PPAT [78] respectively. b Examples of cell cycle proteins found in membrane-less organelles which can undergo phase separation (see Table 1). PONDR disorder prediction plots are shown, indicating prevalence of disordered regions in these proteins (score > 0.5). Coiled coil (CC) and low complexity domains (letters indicate overrepresented amino acids) are also indicated. Phosphotyrosine residues necessary for receptor clustering are indicated for LAT

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References

    1. Zhang HY, et al. RNA controls PolyQ protein phase transitions. Mol Cell. 2015;60:220–230. doi: 10.1016/j.molcel.2015.09.017. - DOI - PMC - PubMed
    1. Altmeyer M, et al. Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose) Nat Commun. 2015;6:8088. doi: 10.1038/ncomms9088. - DOI - PMC - PubMed
    1. Brangwynne CP, et al. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science. 2009;324:1729–1732. doi: 10.1126/science.1172046. - DOI - PubMed
    1. Brangwynne CP, Mitchison TJ, Hyman AA. Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc Natl Acad Sci USA. 2011;108:4334–4339. doi: 10.1073/pnas.1017150108. - DOI - PMC - PubMed
    1. Brangwynne CP, Tompa P, Pappu RV. Polymer physics of intracellular phase transitions. Nat Phys. 2015;11:899–904. doi: 10.1038/nphys3532. - DOI

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