美国肯塔基大学Matthew S. Gentry研究组发现核糖原分解调节人非小细胞肺癌中组蛋白的乙酰化。 该研究2019年9月12日在线发表于国际期刊《细胞—代谢》。
在这项研究中，研究者利用细胞核纯化和稳定同位素示踪来确定核糖原的起源和代谢命运。研究人员通过区室化丙酮酸的产生和组蛋白乙酰化揭示了核糖原在表观遗传调控中的关键功能。该调控途径在人非小细胞肺癌中发生改变，因为在手术标本中发现细胞核中糖原的积累。
研究者证明，通过阻止糖原磷酸化酶的核转移导致核糖原积累，malin（一种E3泛素连接酶）的丰度降低会破坏核糖原分解。在肺癌细胞中重新表达malin恢复了核糖原分解，增加了组蛋白乙酰化，并减少了移植到小鼠体内的癌细胞的生长。该研究揭示了细胞核中糖原代谢的未知作用，并阐明了细胞代谢物控制表观遗传调控的另一种机制。
据了解，核糖原首先在20世纪40年代早期被发现，但其在细胞生理学中的作用仍有待阐明。
附：英文原文
Title: Nuclear Glycogenolysis Modulates Histone Acetylation in Human Non-Small Cell Lung Cancers
Author: Ramon C. Sun, Vikas V. Dukhande, Zhengqiu Zhou, Lyndsay E.A. Young, Shane Emanuelle, Christine Fillmore Brainson, Matthew S. Gentry
Issue&Volume: 12 September 2019
Summary:
Nuclear glycogen was first documented in the early 1940s, but its role in cellular physiology remained elusive. In this study, we utilized pure nuclei preparations and stable isotope tracers to define the origin and metabolic fate of nuclear glycogen. Herein, we describe a key function for nuclear glycogen in epigenetic regulation through compartmentalized pyruvate production and histone acetylation. This pathway is altered in human non-small cell lung cancers, as surgical specimens accumulate glycogen in the nucleus. We demonstrate that the decreased abundance of malin, an E3 ubiquitin ligase, impaired nuclear glycogenolysis by preventing the nuclear translocation of glycogen phosphorylase and causing nuclear glycogen accumulation. Re-introduction of malin in lung cancer cells restored nuclear glycogenolysis, increased histone acetylation, and decreased growth of cancer cells transplanted into mice. This study uncovers a previously unknown role for glycogen metabolism in the nucleus and elucidates another mechanism by which cellular metabolites control epigenetic regulation.
DOI: 10.1016/j.cmet.2019.08.014
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30443-7
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx
本期文章：《细胞—代谢》：Online/在线发表
