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Novel regulation of gene expression in brain tumors identified

Date:
December 6, 2017
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
New study results reveal a previously unknown interplay between two key enzymes and a novel understanding of how brain cancer tumors form and spread.
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Study results revealed previously unknown interplay between two key enzymes and a novel understanding of how brain cancer tumors form and spread, according to researchers at The University of Texas MD Anderson Cancer Center.

The study, led by Zhimin Lu, M.D., Ph.D., professor of Neuro-Oncology, identified a previously unreported linkage between two enzymes known as Gcn5 and alpha-ketoglutarate dehydrogenase (alpha-KGDH), providing important new information about a histone modification process called succinylation. Results were published in the Dec. 6 online issue of Nature.

Histones are proteins vital for gene regulation, and histone modifications are central to regulation of many chromosome-related processes, including DNA replication, transcription and repair. There are 16 known histone modifications, including succinylation. Lu's team studied the alpha-KGDH-generated succinyl-coenzyme A, a molecule crucial for many biochemical reactions in protein, carbohydrate and lipid metabolism, as well as for providing energy to cells.

"Succinylation is a newly identified histone modification; however, the mechanism underlying histone succinylation and its functional consequences are unknown," said Lu. "In our study, we demonstrated that alpha-KGDH, when coupled with Gcn5, induces histone succinylation and promotes tumor cell proliferation and tumor development."

Gcn5 is an enzyme known as a histone acetyltransferase which delivers molecular components making up an acetyl group to histone genes, allowing the genes to be switched on or off. Histones and other proteins, when modified by this process known as acetylation, play critical roles in regulation of gene expression, typically resulting in increased gene expression.

"We demonstrated that alpha-KGDH interacts with Gcn5 in the cell nucleus and found that tumor cell proliferation and tumor growth were inhibited when alpha-KGDH was blocked from entering the cell nucleus or by disruption of Gcn5's binding to succinyl-coenzyme A," said Lu. "These findings underscore the significance of Gcn5-regulated gene expression coupled with the metabolic enzyme alpha-KGDH in tumor cell proliferation and formation."


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Materials provided by University of Texas M. D. Anderson Cancer Center. Note: Content may be edited for style and length.


Journal Reference:

  1. Yugang Wang, Yusong R. Guo, Ke Liu, Zheng Yin, Rui Liu, Yan Xia, Lin Tan, Peiying Yang, Jong-Ho Lee, Xin-jian Li, David Hawke, Yanhua Zheng, Xu Qian, Jianxin Lyu, Jie He, Dongming Xing, Yizhi Jane Tao, Zhimin Lu. KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase. Nature, 2017; DOI: 10.1038/nature25003

Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Novel regulation of gene expression in brain tumors identified." ScienceDaily. ScienceDaily, 6 December 2017. <www.sciencedaily.com/releases/2017/12/171206142339.htm>.
University of Texas M. D. Anderson Cancer Center. (2017, December 6). Novel regulation of gene expression in brain tumors identified. ScienceDaily. Retrieved May 30, 2024 from www.sciencedaily.com/releases/2017/12/171206142339.htm
University of Texas M. D. Anderson Cancer Center. "Novel regulation of gene expression in brain tumors identified." ScienceDaily. www.sciencedaily.com/releases/2017/12/171206142339.htm (accessed May 30, 2024).

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