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范可尼贫血通路的新功能概览。

Emerging functions of the Fanconi anemia pathway at a glance.

作者信息

Sumpter Rhea, Levine Beth

机构信息

Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA

Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.

出版信息

J Cell Sci. 2017 Aug 15;130(16):2657-2662. doi: 10.1242/jcs.204909.

Abstract

Fanconi anemia (FA) is a rare disease, in which homozygous or compound heterozygous inactivating mutations in any of 21 genes lead to genomic instability, early-onset bone marrow failure and increased cancer risk. The FA pathway is essential for DNA damage response (DDR) to DNA interstrand crosslinks. However, proteins of the FA pathway have additional cytoprotective functions that may be independent of DDR. We have shown that many FA proteins participate in the selective autophagy pathway that is required for the destruction of unwanted intracellular constituents. In this Cell Science at a Glance and the accompanying poster, we briefly review the role of the FA pathway in DDR and recent findings that link proteins of the FA pathway to selective autophagy of viruses and mitochondria. Finally, we discuss how perturbations in FA protein-mediated selective autophagy may contribute to inflammatory as well as genotoxic stress.

摘要

范可尼贫血(FA)是一种罕见疾病,其中21个基因中任何一个的纯合或复合杂合失活突变都会导致基因组不稳定、早发性骨髓衰竭和癌症风险增加。FA通路对于DNA双链交联的DNA损伤反应(DDR)至关重要。然而,FA通路的蛋白质具有额外的细胞保护功能,这些功能可能独立于DDR。我们已经表明,许多FA蛋白参与了选择性自噬途径,该途径是破坏不需要的细胞内成分所必需的。在这篇“细胞科学一览”及随附的海报中,我们简要回顾了FA通路在DDR中的作用,以及将FA通路的蛋白质与病毒和线粒体的选择性自噬联系起来的最新发现。最后,我们讨论了FA蛋白介导的选择性自噬的扰动如何可能导致炎症以及基因毒性应激。

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