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癌症中激酶、磷酸酶与微小RNA之间的相互作用。

Crosstalk between kinases, phosphatases and miRNAs in cancer.

作者信息

Abrantes Júlia L F, Tornatore Thaís F, Pelizzaro-Rocha Karin J, de Jesus Marcelo B, Cartaxo Rodrigo T, Milani Renato, Ferreira-Halder Carmen V

机构信息

Department of Biochemistry, Institute of Biology, UNICAMP, 13083-970 Campinas, Brazil.

Department of Biochemistry, Institute of Biology, UNICAMP, 13083-970 Campinas, Brazil.

出版信息

Biochimie. 2014 Dec;107 Pt B:167-87. doi: 10.1016/j.biochi.2014.09.011. Epub 2014 Sep 16.

Abstract

Reversible phosphorylation of proteins, performed by kinases and phosphatases, is the major post translational protein modification in eukaryotic cells. This intracellular event represents a critical regulatory mechanism of several signaling pathways and can be related to a vast array of diseases, including cancer. Cancer research has produced increasing evidence that kinase and phosphatase activity can be compromised by mutations and also by miRNA silencing, performed by small non-coding and endogenously produced RNA molecules that lead to translational repression. miRNAs are believed to target about one-third of human mRNAs while a single miRNA may target about 200 transcripts simultaneously. Regulation of the phosphorylation balance by miRNAs has been a topic of intense research over the last years, spanning topics going as far as cancer aggressiveness and chemotherapy resistance. By addressing recent studies that have shown miRNA expression patterns as phenotypic signatures of cancers and how miRNA influence cellular processes such as apoptosis, cell cycle control, angiogenesis, inflammation and DNA repair, we discuss how kinases, phosphatases and miRNAs cooperatively act in cancer biology.

摘要

由激酶和磷酸酶执行的蛋白质可逆磷酸化是真核细胞中主要的翻译后蛋白质修饰。这种细胞内事件代表了几种信号通路的关键调节机制,并且可能与包括癌症在内的大量疾病有关。癌症研究已经产生了越来越多的证据表明,激酶和磷酸酶活性可能会因突变以及由导致翻译抑制的小的非编码内源性RNA分子进行的miRNA沉默而受到损害。据信,miRNA靶向约三分之一的人类mRNA,而单个miRNA可能同时靶向约200个转录本。在过去几年中,miRNA对磷酸化平衡的调节一直是深入研究的主题,涵盖了诸如癌症侵袭性和化疗抗性等主题。通过探讨最近的研究,这些研究表明miRNA表达模式作为癌症的表型特征以及miRNA如何影响细胞过程,如细胞凋亡、细胞周期控制、血管生成、炎症和DNA修复,我们讨论了激酶、磷酸酶和miRNA如何在癌症生物学中协同作用。

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