Biomolecular Condensates and Cancer

Boija, Ann; Klein, I.; Young, Richard A.

doi:10.1016/j.ccell.2020.12.003

Cited by 187 publications

(176 citation statements)

References 302 publications

(362 reference statements)

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“… 41 Thus, these drugs encounter their targets in the nuclear condensates containing transcription factors and proteins involved in RNA processing. The disturbance of biomolecular condensates in the nucleus was linked to oncogenesis, 39 and understanding of these processes is expected to provide new therapeutic tools.…”

Section: Discussionmentioning

confidence: 99%

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands

et al. 2021

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“…Numerous cancer-related proteins that may be involved in migration, invasion, and metastasis are localized in lipid rafts, understood to be signaling hubs for these proteins [ 104 , 105 , 106 ]. Gene transcription has been shown to be regulated by biomolecular condensates [ 107 , 108 , 109 ]; therefore, the recent association of mutations in cancer-related genes with aberrant phase-separated biomolecular condensates [ 10 , 110 ] emphasizes essential relationships between membranes, lipid rafts, and ATP that may not be fully elucidated.…”

Section: The Interdependence Between Membranes and Membraneless Organellesmentioning

confidence: 99%

“…LLPS creates distinct compartments that enhance or restrict biochemical reactions by enriching or excluding biomolecules from their environment [ 7 ]. Increasing evidence associates diseases such as neurodegeneration and cancer with the formation of protein aggregates from dysregulated, aberrant transitions in phase separation [ 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

Loh¹,

Reíter

2021

Antioxidants

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Biomolecular condensates are membraneless organelles (MLOs) that form dynamic, chemically distinct subcellular compartments organizing macromolecules such as proteins, RNA, and DNA in unicellular prokaryotic bacteria and complex eukaryotic cells. Separated from surrounding environments, MLOs in the nucleoplasm, cytoplasm, and mitochondria assemble by liquid–liquid phase separation (LLPS) into transient, non-static, liquid-like droplets that regulate essential molecular functions. LLPS is primarily controlled by post-translational modifications (PTMs) that fine-tune the balance between attractive and repulsive charge states and/or binding motifs of proteins. Aberrant phase separation due to dysregulated membrane lipid rafts and/or PTMs, as well as the absence of adequate hydrotropic small molecules such as ATP, or the presence of specific RNA proteins can cause pathological protein aggregation in neurodegenerative disorders. Melatonin may exert a dominant influence over phase separation in biomolecular condensates by optimizing membrane and MLO interdependent reactions through stabilizing lipid raft domains, reducing line tension, and maintaining negative membrane curvature and fluidity. As a potent antioxidant, melatonin protects cardiolipin and other membrane lipids from peroxidation cascades, supporting protein trafficking, signaling, ion channel activities, and ATPase functionality during condensate coacervation or dissolution. Melatonin may even control condensate LLPS through PTM and balance mRNA- and RNA-binding protein composition by regulating N6-methyladenosine (m6A) modifications. There is currently a lack of pharmaceuticals targeting neurodegenerative disorders via the regulation of phase separation. The potential of melatonin in the modulation of biomolecular condensate in the attenuation of aberrant condensate aggregation in neurodegenerative disorders is discussed in this review.

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“…CRCmapper was successfully used to map core TRNs in normal [20] , [106] or cancer samples [107] , [108] . Importantly, as SEs cluster in the cell to form phase-separated condensates, these can be targeted with drugs to rewire transcriptional addictions in cancer [109] , [110] , [111] .…”

Section: Modelling Trns From Other Data Types or Integrating Multiple Data Typesmentioning

confidence: 99%

Computational biology approaches for mapping transcriptional regulatory networks

Saint-André

2021

Computational and Structural Biotechnology Journal

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Biomolecular Condensates and Cancer

Cited by 187 publications

References 302 publications

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands

Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders

Computational biology approaches for mapping transcriptional regulatory networks

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