林28
生物
翻译(生物学)
小RNA
RNA结合蛋白
生物发生
RNA剪接
核糖核酸
心理压抑
信使核糖核酸
锌指
细胞生物学
秀丽隐杆线虫
选择性拼接
计算生物学
遗传学
基因
基因表达
胚胎干细胞
转录因子
诱导多能干细胞
作者
Greater Kayode Oyejobi,Xiaodan Yan,Piotr Sliz,Longfei Wang
摘要
Originally discovered in C. elegans, LIN28 is an evolutionarily conserved zinc finger RNA-binding protein (RBP) that post-transcriptionally regulates genes involved in developmental timing, stem cell programming, and oncogenesis. LIN28 acts via two distinct mechanisms. It blocks the biogenesis of the lethal-7 (let-7) microRNA (miRNA) family, and also directly binds messenger RNA (mRNA) targets, such as IGF-2 mRNA, and alters downstream splicing and translation events. This review focuses on the molecular mechanism of LIN28 repression of let-7 and current strategies to overcome this blockade for the purpose of cancer therapy. We highlight the value of the LIN28/let-7 pathway as a drug target, as multiple oncogenic proteins that the pathway regulates are considered undruggable due to their inaccessible cellular location and lack of cavities for small molecule binding.
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