4.6 Review

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

Journal

AMERICAN JOURNAL OF CANCER RESEARCH
Volume 11, Issue 8, Pages 3766-3776

Publisher

E-CENTURY PUBLISHING CORP

Keywords

Liquid-liquid phase separation; membraneless condensates; modular domains; intrinsically disordered regions

Categories

Funding

  1. Ministry of Science and Technology Summit and Frontier grants [108-2321-B-182A-005, 109-2326-B-182A-002, 109-2628-B-039-006, 109-2320-B-182A-022]
  2. Chang Gung Memorial Hospital [OMRPG3I0012, NMRPG3J6192, CORPG3J0232, NMRPG3J0672, NMRPG3K0511]
  3. China Medical Univer-sity [CMU109-MF-12]

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LLPS is a mechanism used to explain the formation of organelles and membraneless condensates, facilitating multiple biological processes. Dysfunction of LLPS may lead to disease formation, and it plays a role in regulating normal cellular physiology and contributing to tumorigenesis.
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.

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