Liquid–liquid phase separation in tumor biology
TLDR
In this article , the authors comprehensively summarize the detailed mechanisms of biomolecular condensate formation and biophysical function and review the recent major advances toward elucidating the multiple mechanisms involved in cancer cell pathology driven by aberrant liquid-liquid phase separation (LLPS).Abstract:
Liquid-liquid phase separation (LLPS) is a novel principle for explaining the precise spatial and temporal regulation in living cells. LLPS compartmentalizes proteins and nucleic acids into micron-scale, liquid-like, membraneless bodies with specific functions, which were recently termed biomolecular condensates. Biomolecular condensates are executors underlying the intracellular spatiotemporal coordination of various biological activities, including chromatin organization, genomic stability, DNA damage response and repair, transcription, and signal transduction. Dysregulation of these cellular processes is a key event in the initiation and/or evolution of cancer, and emerging evidence has linked the formation and regulation of LLPS to malignant transformations in tumor biology. In this review, we comprehensively summarize the detailed mechanisms of biomolecular condensate formation and biophysical function and review the recent major advances toward elucidating the multiple mechanisms involved in cancer cell pathology driven by aberrant LLPS. In addition, we discuss the therapeutic perspectives of LLPS in cancer research and the most recently developed drug candidates targeting LLPS modulation that can be used to combat tumorigenesis. read more
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Landscape of semi-extractable RNAs across five human cell lines
TL;DR: More than 1,325 semi-extractable RNAs were identified across five humancell lines, including NEAT1, TRIO, EXT1, ZCCHC7, and FTX, which exhibited stable semi- Extraction, implying that RNAs in this group are potential candidates of architectural RNAs that constitute nuclear bodies.
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Targeting phase separation on enhancers induced by transcription factor complex formations as a new strategy for treating drug-resistant cancers
Ken-ichi Takayama,Satoshi Inoue +1 more
TL;DR: It is proposed that repression of TF collaborations involved in the LLPS of SEs could be a promising strategy for advanced cancer therapy.
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Role of condensates in modulating DNA repair pathways and its implication for chemoresistance
Giuseppe Dall’Agnese,Alessandra Dall’Agnese,Salman F. Banani,Marta Codrich,Matilde Clarissa Malfatti,Giulia Antoniali,Gianluca Tell +6 more
TL;DR: In this paper , the authors summarize key features of biomolecular condensates and note where they have been implicated in the repair of DNA double-strand breaks, including nucleotide modifications, and bulky lesions, among others.
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The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease
TL;DR: Current knowledge on the link between AR repeat polymorphisms and cancer types is summarized, including mechanistic explanations and models comprising the relationship between condensate formation, polyQ1 length and transcriptional activity are summarized.
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Liquid–Liquid Phase Separation of Biomacromolecules and Its Roles in Metabolic Diseases
TL;DR: This review aims to expound on the current concept and methods of LLPS and summarize its vital roles in T2DM, AD, and MBDs, uncover novel mechanisms of these metabolic diseases, and thus provide powerful potential therapeutic strategies and targets for ameliorating these metabolic Diseases.
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Journal ArticleDOI
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TL;DR: A cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains is reported, establishing proof-of-concept for targeting protein–protein interactions of epigenetic ‘readers’, and providing a versatile chemical scaffold for the development of chemical probes more broadly throughout the b romodomain family.