Ubiquitin‐Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?. (3rd September 2020)

• Record Type: Journal Article
• Authors: Dao, Thuy P.; Castañeda, Carlos A.
• Is Part Of: BioEssays. Volume 42:Number 11(2020:Nov.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-09-03
• Subjects: autophagy -- biomolecular condensates -- liquid‐liquid phase separation -- polyubiquitin -- proteasomal degradation -- protein quality control -- ubiquitin shuttle proteins; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202000036
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: Liquid‐liquid phase separation (LLPS) has recently emerged as a possible mechanism that enables ubiquitin‐binding shuttle proteins to facilitate the degradation of ubiquitinated substrates via distinct protein quality control (PQC) pathways. Shuttle protein LLPS is modulated by multivalent interactions among their various domains as well as heterotypic interactions with polyubiquitin chains. Here, the properties of three different shuttle proteins (hHR23B, p62, and UBQLN2) are closely examined, unifying principles for the molecular determinants of their LLPS are identified, and how LLPS is connected to their functions is discussed. Evidence supporting LLPS of other shuttle proteins is also found. In this review, it is proposed that shuttle protein LLPS leads to spatiotemporal regulation of PQC activities by mediating the recruitment of PQC machinery (including proteasomes or autophagic components) to biomolecular condensates, assembly/disassembly of condensates, selective enrichment of client proteins, and extraction of ubiquitinated proteins from condensates in cells. Abstract : Ubiquitin‐binding shuttle proteins are essential for both proteasomal degradation and autophagy. Recent studies show that polyubiquitin chains modulate the ability of shuttle proteins to undergo liquid‐liquid phase separation (LLPS). Here, the unifying principles of shuttle protein LLPS, and functional implications of LLPS on protein quality control mechanisms are discussed.