HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma.
HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma.
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PKM2 的 HDAC8 依赖性脱乙酰作用指导核定位和糖酵解，以促进肝细胞癌的增殖。
DOI：
10.1038/s41419-020-03212-3
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发表时间：
2020-12-05
影响因子：
9
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Zhang R;Shen M;Wu C;Chen Y;Lu J;Li J;Zhao L;Meng H;Zhou X;Huang G;Zhao X;Liu J
丙酮酸激酶 M2 (PKM2) 不仅是指导糖酵解的关键限速酶，而且还作为调节基因转录的非代谢蛋白。近年来一系列研究证实，翻译后修饰已成为调节PKM2功能的重要机制，进而影响肿瘤发生。在本研究中，我们发现K62残基被脱乙酰化，这与HCC的预后有关。进一步的研究表明 HDAC8 结合 PKM2 的 K62 残基并使其去乙酰化。从机制上讲，K62 去乙酰化促进 PKM2 转运到细胞核并结合 β-catenin，从而促进 CCND1 基因转录和细胞周期进程。此外，K62的脱乙酰化影响PKM2的酶活性和葡萄糖代谢通量。因此，这些结果表明HDAC8/PKM2信号传导可能成为HCC治疗的新靶点。
Pyruvate kinase M2 (PKM2) is not only a key rate-limiting enzyme that guides glycolysis, but also acts as a non-metabolic protein in regulating gene transcription. In recent years, a series of studies have confirmed that post-translational modification has become an important mechanism for regulating the function of PKM2, which in turn affects tumorigenesis. In this study, we found that K62 residues were deacetylated, which is related to the prognosis of HCC. Further studies indicate that HDAC8 binds and deacetylates the K62 residue of PKM2. Mechanistically, K62 deacetylation facilitate PKM2 transport into the nucleus and bind β-catenin, thereby promoting CCND1 gene transcription and cell cycle progression. In addition, the deacetylation of K62 affects the enzyme activity of PKM2 and the flux of glucose metabolism. Therefore, these results suggest that HDAC8 / PKM2 signaling may become a new target for the treatment of HCC.
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影响因子：
11.2
作者：
Park SH;Ozden O;Liu G;Song HY;Zhu Y;Yan Y;Zou X;Kang HJ;Jiang H;Principe DR;Cha YI;Roh M;Vassilopoulos A;Gius D
通讯作者：
Gius D
影响因子：
37.3
作者：
Hsu MC;Hung WC
通讯作者：
Hung WC
影响因子：
21.3
作者：
Liu F;Ma F;Wang Y;Hao L;Zeng H;Jia C;Wang Y;Liu P;Ong IM;Li B;Chen G;Jiang J;Gong S;Li L;Xu W
通讯作者：
Xu W
K433 乙酰化的促有丝分裂和致癌刺激可促进 PKM2 蛋白激酶活性和核定位。
影响因子：
16
作者：
Lv, Lei;Xu, Yan-Ping;Xiong, Yue
通讯作者：
Xiong, Yue
影响因子：
11.2
作者：
Tian, Yuan;Wong, Vincent W. S.;Chan, Henry L. Y.
通讯作者：
Chan, Henry L. Y.