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Aberrant phase separation and cancer
Taniue, Kenzui ; Akimitsu, Nobuyoshi
The FEBS journal, 2022-01, Vol.289 (1), p.17-39
[Periódico revisado por pares]
England: Blackwell Publishing Ltd
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Título:
Aberrant phase separation and cancer
Autor:
Taniue, Kenzui
;
Akimitsu, Nobuyoshi
Assuntos:
Aberration
;
Agglomeration
;
Amyloid
;
Cancer
;
Compartments
;
Condensates
;
Cytoplasm - genetics
;
Cytoplasm - metabolism
;
Drug development
;
drug targeting phase separation and transition
;
Eukaryotic Cells - metabolism
;
fusion protein
;
Humans
;
Lipid bilayers
;
Lipid Bilayers - metabolism
;
Lipids
;
Liquid phases
;
low‐complexity regions
;
Macromolecules
;
Mutation
;
Mutation - genetics
;
Neoplasms - genetics
;
Neoplasms - pathology
;
Neurodegeneration
;
oncogenic mutation
;
Organelles
;
Organelles - genetics
;
Organelles - metabolism
;
Phase separation
;
phase separation/transition
;
Phase Transition
;
Phase transitions
;
Proteins
;
Regulatory mechanisms (biology)
;
signal transduction
;
transcription
;
Tumorigenesis
É parte de:
The FEBS journal, 2022-01, Vol.289 (1), p.17-39
Descrição:
Eukaryotic cells are intracellularly divided into numerous compartments or organelles, which coordinate specific molecules and biological reactions. Membrane‐bound organelles are physically separated by lipid bilayers from the surrounding environment. Biomolecular condensates, also referred to membraneless organelles, are micron‐scale cellular compartments that lack membranous enclosures but function to concentrate proteins and RNA molecules, and these are involved in diverse processes. Liquid–liquid phase separation (LLPS) driven by multivalent weak macromolecular interactions is a critical principle for the formation of biomolecular condensates, and a multitude of combinations among multivalent interactions may drive liquid–liquid phase transition (LLPT). Dysregulation of LLPS and LLPT leads to aberrant condensate and amyloid formation, which causes many human diseases, including neurodegeneration and cancer. Here, we describe recent findings regarding abnormal forms of biomolecular condensates and aggregation via aberrant LLPS and LLPT of cancer‐related proteins in cancer development driven by mutation and fusion of genes. Moreover, we discuss the regulatory mechanisms by which aberrant LLPS and LLPT occur in cancer and the drug candidates targeting these mechanisms. Further understanding of the molecular events regulating how biomolecular condensates and aggregation form in cancer tissue is critical for the development of therapeutic strategies against tumorigenesis. Dysregulation of liquid–liquid phase separation (LLPS) and liquid–liquid phase transition (LLPT) leads to aberrant biomolecular condensate and amyloid formation, which causes cancer development. Here, we describe the emerging concept of aberrant biomolecular condensates and aggregation driven by mutation and fusion‐derived aberrant LLPS and LLPT in cancer. Moreover, we discuss the regulatory mechanisms by which aberrant LLPS and LLPT occur in cancer and the drug candidates targeting these mechanisms.
Editor:
England: Blackwell Publishing Ltd
Idioma:
Inglês
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