Nucleoli and Promyelocytic Leukemia Protein (PML) bodies are phase separated nuclear protein quality control compartments for misfolded proteins

L Mediani; J Guillén-Boixet; S Alberti; S Carra

doi:10.1080/23723556.2019.1652519

Nucleoli and Promyelocytic Leukemia Protein (PML) bodies are phase separated nuclear protein quality control compartments for misfolded proteins

Mol Cell Oncol. 2019 Aug 26;6(6):e1415624. doi: 10.1080/23723556.2019.1652519. eCollection 2019.

Authors

L Mediani¹, J Guillén-Boixet², S Alberti^{2

3}, S Carra¹

Affiliations

¹ Centre for Neuroscience and Nanotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
² Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
³ Technische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Biotechnology Center (BIOTEC), Dresden, Germany.

Abstract

We uncovered a role for nucleoli and PML-bodies as phase-separated protein quality control organelles that compartmentalize protein quality control factors and misfolded proteins for their efficient clearance. Failure to dispose misfolded proteins converts nucleoli and PML-bodies into a solid state that immobilizes ubiquitin, limiting its recycling for genome integrity maintenance.

Keywords: Protein quality control; genome instability; membraneless organelles; nucleus.

Grants and funding

S.C. acknowledges AriSLA Foundation (Granulopathy and MLOpathy); Cariplo Foundation (Rif. 2014-0703); MAECI (Dissolve_ALS); and MIUR (Departments of excellence 2018–2022; E91I18001480001). S.C. and S.A. acknowledge EU Joint Programme—Neurodegenerative Disease Research (JPND) project. The project is supported through funding organizations under the aegis of JPND (http://www.neurodegenerationresearch.eu/). This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 643417. S.A. acknowledges the Max Planck Society, the ERC (no. 725836), and the BMBF (01ED1601A, 031A359A).