@article{dad8539af2de48aaa34442c6adc63c6f,
title = "Lysine acetylation activates 6-phosphogluconate dehydrogenase to promote tumor growth",
abstract = "Although the oxidative pentose phosphate pathway is important for tumor growth, how 6-phosphogluconate dehydrogenase (6PGD) in this pathway is upregulated in human cancers is unknown. We found that 6PGD is commonly activated in EGF-stimulated cells and human cancer cells by lysine acetylation. Acetylation at K76 and K294 of 6PGD promotes NADP+ binding to 6PGD and formation of active 6PGD dimers, respectively. Moreover, we identified DLAT and ACAT2 as upstream acetyltransferases of K76 and K294, respectively, and HDAC4 as the deacetylase of both sites. Expressing acetyl-deficient mutants of 6PGD in cancer cells significantly attenuated cell proliferation and tumor growth. This is due in partto reduced levels of 6PGD products ribulose-5-phosphate and NADPH, which led to reduced RNA and lipid biosynthesis as well as elevated ROS. Furthermore, 6PGD activity is upregulated with increased lysine acetylation in primary leukemia cells from human patients, providing mechanistic insights into 6PGD upregulation in cancer cells.",
author = "Changliang Shan and Shannon Elf and Quanjiang Ji and Kang, {Hee Bum} and Lu Zhou and Taro Hitosugi and Lingtao Jin and Ruiting Lin and Liang Zhang and Seo, {Jae Ho} and Jianxin Xie and Meghan Tucker and Gu, {Ting Lei} and Jessica Sudderth and Lei Jiang and DeBerardinis, {Ralph J.} and Shaoxiong Wu and Yuancheng Li and Hui Mao and Chen, {Peng R.} and Dongsheng Wang and Chen, {Georgia Zhuo} and Sagar Lonial and Arellano, {Martha L.} and Khoury, {Hanna J.} and Khuri, {Fadlo R.} and Lee, {Benjamin H.} and Brat, {Daniel J.} and Keqiang Ye and Boggon, {Titus J.} and Chuan He and Sumin Kang and Jun Fan and Jing Chen",
note = "Funding Information: We thank Susan Sunay at the Hematology Division Tissue Bank, Winship Cancer Institute of Emory, for providing primary tissue samples from leukemia patients. This work was supported in part by NIH grants CA140515, CA183594, CA174786 (J.C.), CA175316 (S.K.), and GM071440 (C.H.) and by the Pharmacological Sciences Training Grant T32 GM008602 (S.E.), DoD grant W81XWH-12-1-0217 (J.C.), National Natural Science Funds of China number 20902013 (L.Z.), Charles Harris Run For Leukemia, Inc. (H.J.K.), and the Hematology Tissue Bank of the Emory University School of Medicine and the Georgia Cancer Coalition (H.J.K.). J.X., M.T., and T.-L.G. are employees of Cell Signaling Technology, Inc. H.J.K., F.R.K., S.K., and J.C. are Georgia Cancer Coalition Distinguished Cancer Scholars. S.K. is a Robbins Scholar. S.K. and J.C. are American Cancer Society Basic Research Scholars. J.C. is a Scholar of the Leukemia and Lymphoma Society. ",
year = "2014",
month = aug,
day = "21",
doi = "10.1016/j.molcel.2014.06.020",
language = "English (US)",
volume = "55",
pages = "552--565",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",
}