Liquid-liquid phase separation (LLPS) in cellular physiology and tumor biology.

TLDR

LLPS explains the formation of membraneless organelles such as nucleoli, PML bodies, and stress granules, and is implicated in processes including transcription, chromatin organization, DNA damage response, autophagy, and tumorigenesis. This review aims to summarize the principles and components of LLPS and discuss its regulatory roles in normal cellular physiology and tumorigenesis. The authors describe how LLPS, driven by proteins with modular domains or intrinsically disordered regions and nucleic acids, forms condensates that regulate diverse biological processes and whose disruption can lead to disease.

Abstract

Liquid-liquid phase separation (LLPS) has emerged as a mechanism that has been used to explain the formation of known organelles (e.g. nucleoli, promyelocytic leukemia nuclear bodies (PML NBs), etc) as well as other membraneless condensates (e.g. nucleosome arrays, DNA damage foci, X-chromosome inactivation (XCI) center, paraspeckles, stress granules, proteasomes, autophagosomes, etc). The formation of membraneless condensates could be triggered by proteins containing modular domains or intrinsically disordered regions (IDRs) and nucleic acids. Multiple biological processes including transcription, chromatin organization, X-chromosome inactivation (XCI), DNA damage, tumorigenesis, autophagy, etc have been shown to utilize the principle of LLPS to facilitate these processes. This review will summarize the principle and components of LLPS, and describe how LLPS regulate these numerous biological processes and disruption of LLPS would cause disease formation. The role of LLPS in regulating normal cellular physiology and contributing to tumorigenesis will be discussed.