Annexin A2 is a novel cellular redox regulatory protein involved in tumorigenesis.
Annexin A2 is a novel cellular redox regulatory protein involved in tumorigenesis.
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DOI：
10.18632/oncotarget.375
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Waisman DM
中科院分区：
文献类型：
--
作者：
Madureira PA;Hill R;Miller VA;Giacomantonio C;Lee PW;Waisman DM
膜联蛋白是一个结构相关的钙和磷脂结合蛋白家族，参与调节广泛的分子和细胞过程。膜联蛋白A2在膜联蛋白中是独特的，因为它具有氧化还原敏感的半胱氨酸。ANXA 2在细胞中的普遍和丰富的表达及其与过氧化氢的反应性使我们假设这种蛋白质可能在细胞氧化还原调节中发挥作用。在这里，我们表明ANXA 2蛋白水平是由过氧化氢诱导的。此外，ANXA 2的耗尽导致氧化应激后细胞活性氧簇（ROS）升高，ROS诱导的促凋亡激酶JNK、p38和Akt的激活增加，以及对ROS介导的细胞损伤/死亡的敏感性升高。与WT小鼠相比，ANXA 2基因敲除小鼠的肝脏和肺组织中的蛋白质氧化显著升高。与对照组相比，ANXA 2缺失的癌细胞表现出细胞蛋白质氧化增强，同时肿瘤生长减少，抗氧化剂N-乙酰半胱氨酸可逆转细胞蛋白质氧化和肿瘤生长缺陷，表明ANXA 2在肿瘤发生过程中调节细胞氧化还原中起关键作用。离体人类癌症研究表明，ANXA 2还原形式的上调与保护肿瘤蛋白免受氧化有关。总之，我们的研究结果表明，ANXA 2通过保护细胞免受氧化应激，在细胞氧化还原调节中发挥重要作用，这种作用在肿瘤发生过程中特别重要。
Annexins are a structurally related family of calcium and phospholipid-binding proteins that are involved in the regulation of a wide range of molecular and cellular processes. Annexin A2 is unique among the annexins in that it possesses redox sensitive cysteine(s). The ubiquitous and abundant expression of ANXA2 in cells and its reactivity with hydrogen peroxide led us to hypothesize that this protein could play a role in cellular redox regulation. Here we show that ANXA2 protein levels are induced by hydrogen peroxide. Furthermore, depletion of ANXA2 resulted in the elevation of cellular reactive oxygen species (ROS) upon oxidative stress, increased activation of the ROS-induced pro-apoptotic kinases, JNK, p38 and Akt and elevated sensitivity to ROS-mediated cellular damage/death. ANXA2-null mice showed significantly elevated protein oxidation in the liver and lung tissues compared to WT mice. ANXA2 depleted cancer cells showed enhanced cellular protein oxidationconcomitant with decreased tumor growth compared to control cancer cells andboth the oxidation of cellular proteins and tumor growth deficit werereversed by the antioxidant N-acetyl cysteine, indicating that ANXA2 plays akey role in the regulation of cellular redox during tumorigenesis. Ex-vivo human cancer studies showed that up-regulation of the reduced form of ANXA2 is associated with protection of the tumor proteins from oxidation. In summary, our results indicate that ANXA2 plays an important role incellular redox regulation by protecting cells from oxidative stress, aneffect that is particularly important during tumorigenesis.
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影响因子：
50.3
作者：
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通讯作者：
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