GAPDH mediates nitrosylation of nuclear proteins.
GAPDH mediates nitrosylation of nuclear proteins.
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DOI：
10.1038/ncb2114
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发表时间：
2010-11
影响因子：
21.3
通讯作者：
Snyder, Solomon H.
中科院分区：
文献类型：
--
作者：
Kornberg, Michael D.;Sen, Nilkantha;Hara, Makoto R.;Juluri, Krishna R.;Nguyen, Judy Van K.;Snowman, Adele M.;Law, Lindsey;Hester, Lynda D.;Snyder, Solomon H.
通过一氧化氮（NO）的S-亚硝基化是向细胞蛋白质发出信号的主要模式，包括突出的核蛋白如HDAC 2和PARP 1。NO基团与蛋白质硫醇的高反应性意味着存在选择性靶向机制。NO信号传导的特异性通常通过NO合酶（NOS）直接或通过支架蛋白如PSD-95和CAPON与靶蛋白的结合来实现。由于NOS的三种主要亚型-神经元NOS（nNOS）、内皮NOS（eNOS）和诱导型NOS（iNOS）-主要是非核的，因此核蛋白被选择性亚硝基化的机制一直是难以捉摸的。甘油醛-3-磷酸脱氢酶（GAPDH）在其Cys 150残基处生理性地亚硝基化，赋予其结合Siah 1的能力，Siah 1具有核定位信号并将亚硝基化GAPDH（SNO-GAPDH）传递到核。我们现在表明，SNO-GAPDH生理转亚硝基化核蛋白，包括脱乙酰酶SIRT 1，组蛋白脱乙酰酶-2（HDAC 2），和DNA激活的蛋白激酶（DNA-PK）。我们的研究结果揭示了一种新的机制，有针对性的亚硝基化的核蛋白，并建议蛋白质-蛋白质转移的NO基团可能是一种通用的机制，在细胞信号转导。
S-nitrosylation by nitric oxide (NO) is a major mode of signaling to cellular proteins, including prominent nuclear proteins such as HDAC2 and PARP1. The high reactivity of the NO group with protein thiols implies the existence of selective targeting mechanisms. Specificity of NO signaling is often achieved by the binding of NO synthase (NOS) to target proteins, either directly or through scaffolding proteins such as PSD-95 and CAPON. As the three principal isoforms of NOS - neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) - are primarily non-nuclear, the mechanisms by which nuclear proteins are selectively nitrosylated have been elusive. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is physiologically nitrosylated at its Cys150 residue, conferring upon it the ability to bind to Siah1, which possesses a nuclear localization signal and conveys nitrosylated GAPDH (SNO-GAPDH) to the nucleus. We now show that SNO-GAPDH physiologically transnitrosylates nuclear proteins, including the deacetylating enzyme SIRT1, histone deacetylase-2 (HDAC2), and DNA-activated protein kinase (DNA-PK). Our findings reveal a novel mechanism for targeted nitrosylation of nuclear proteins and suggest that protein-protein transfer of NO groups may be a general mechanism in cellular signal transduction.
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影响因子：
16
作者：
Nakamura T;Wang L;Wong CC;Scott FL;Eckelman BP;Han X;Tzitzilonis C;Meng F;Gu Z;Holland EA;Clemente AT;Okamoto S;Salvesen GS;Riek R;Yates JR 3rd;Lipton SA
通讯作者：
Lipton SA
影响因子：
4.8
作者：
Gobeil, Fernand, Jr.;Zhu, Tang;Chemtob, Sylvain
通讯作者：
Chemtob, Sylvain
DOI：
10.1073/pnas.0704898104
发表时间：
2007-07-10
影响因子：
11.1
作者：
Mitchell, Douglas A.;Morton, Sarah U.;Marletta, Michael A.
通讯作者：
Marletta, Michael A.
影响因子：
4.7
作者：
MEYERSIEGLER, K;RAHMANMANSUR, N;SIROVER, MA
通讯作者：
SIROVER, MA
影响因子：
5.5
作者：
Jagnandan, D;Sessa, WC;Fulton, D
通讯作者：
Fulton, D