The Role of Phase-Separated Condensates in Fusion Oncoprotein–Driven Cancers
The Role of Phase-Separated Condensates in Fusion Oncoprotein–Driven Cancers
复制标题
相分离凝聚物在融合癌蛋白驱动的癌症中的作用
DOI：
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发表时间：
2023
影响因子：
7.7
通讯作者：
R. Kriwacki
中科院分区：
文献类型：
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作者：
Hazheen K. Shirnekhi;Bappaditya Chandra;R. Kriwacki
由框内染色体易位产生的融合癌蛋白（FO）与许多侵袭性癌症相关，患者预后不良。现在理解几种FO在通过液-液相分离（LLPS）形成的生物分子冷凝物内执行其致癌功能。已经出现了两类相分离FO，形成核凝聚物并改变染色质生物学（包括基因表达）的那些，以及形成细胞质凝聚物并促进异常信号传导（包括RAS/MAPK信号传导）的那些。这些类别内的FO的氨基酸序列显示LLPS倾向的固有无序区域和折叠结构域，其与自身和其他生物分子协同相互作用以促进冷凝物形成。本文综述了LLPS在这两类FO的致癌功能中的作用，提供了抑制正常细胞中生理LLPS的FO的例子，并讨论了通常与LLPS相关的序列特征及其在许多FO中的富集。《癌症生物学年度评论》第7卷的预计最终在线出版日期为2023年4月。请访问http://www.annualreviews.org/page/journal/pubdates了解修订后的估计数。
Fusion oncoproteins (FOs) resulting from in-frame chromosomal translocations are associated with many aggressive cancers with poor patient outcomes. Several FOs are now understood to perform their oncogenic functions within biomolecular condensates formed through liquid-liquid phase separation (LLPS). Two classes of phase-separating FOs have emerged, those that form nuclear condensates and alter chromatin biology, including gene expression, and those that form cytoplasmic condensates and promote aberrant signaling, including RAS/MAPK signaling. The amino acid sequences of the FOs within these classes display LLPS-prone intrinsically disordered regions and folded domains that synergistically interact with themselves and other biomolecules to promote condensate formation. This review summarizes the roles of LLPS in the oncogenic functions of these two FO classes, provides examples of FOs that inhibit physiological LLPS in normal cells, and discusses the sequence features commonly associated with LLPS and their enrichment in many FOs. Expected final online publication date for the Annual Review of Cancer Biology, Volume 7 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.