daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.
daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.
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daf-31 编码 N α-乙酰转移酶的催化亚基，调节秀丽隐杆线虫的发育、代谢和成年寿命。
DOI：
10.1371/journal.pgen.1004699
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发表时间：
2014-10
期刊：
影响因子：
4.5
通讯作者：
Jia K
中科院分区：
文献类型：
--
作者：
Chen D;Zhang J;Minnerly J;Kaul T;Riddle DL;Jia K
秀丽隐杆线虫幼虫为兼性滞育。已经报道了影响dauer信号转导和形态发生的突变。其中，大多数导致dauer幼虫组成型形成的是温度敏感的（ts）。daf-31突变体是在遗传筛选中分离出来的，寻找新的和代表性不足的突变体类别，这些突变体无条件地形成dauer和dauer样幼虫。Dauer样幼虫在发育过程中被阻止，并具有一些但不是全部的正常Dauer特征。我们在这里表明，daf-31突变体形成dauer样幼虫饥饿条件下，但SDS处理敏感。此外，在daf-31突变体中，代谢转向脂肪积累。我们克隆了daf-31基因，它编码一种抑制缺陷蛋白1（ARD 1）的直系同源物，ARD 1是主要N α-乙酰转移酶（NatA）的催化亚基。daf-31启动子：：GFP报告基因表明daf-31在多种组织中表达，包括神经元、咽、肠和皮下细胞。有趣的是，daf-31的过表达增强了daf-2突变体的寿命表型，这取决于叉头转录因子（FOXO）DAF-16。我们证明，daf-31的过表达刺激转录活性，而不影响其亚细胞定位的α-16。这些数据揭示了NatA在控制C.研究表明，ARD 1与FOXO转录因子之间存在着相互作用，这可能有助于理解ARD 1在哺乳动物中的功能。生物体的发育受到环境条件的影响，如营养物质的可用性。在饥饿条件下，C.线虫幼虫会进入一个特殊的发育阶段，称为dauer幼虫。胰岛素样信号通路通过抑制FOXO转录因子β-16的活性来控制dauer形成以及成年寿命，FOXO转录因子β-16调节抗应激基因的表达。在这里，我们分离出一个新的基因，称为daf-31;这个基因编码一种蛋白质，调节C。线虫幼虫发育、代谢和成虫寿命。这种蛋白质在其他物种中被发现是一种酶的一部分，可以修饰其他蛋白质。我们发现，我们的新发现的蛋白质的过表达刺激转录活性的α-16。有趣的是，与α-31类似的人类蛋白质的异常调节导致肿瘤形成。已知人FOXO蛋白防止肿瘤发生。因此，有可能异常的α-31活性可能通过降低α-16活性而导致肿瘤生长。因此，本研究不仅有助于了解一种通用酶在控制蠕虫以外的其他生物体的发育、代谢和寿命方面的作用，而且还可能揭示人类肿瘤发生的机制。
The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts). The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1) that is the catalytic subunit of the major N alpha-acetyltransferase (NatA). A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO) DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals. The development of a living organism is influenced by the environmental conditions such as nutrient availability. Under starvation conditions, the C. elegans larvae will enter a special developmental stage called dauer larva. An insulin-like signaling pathway controls dauer formation as well as adult lifespan by inhibiting the activity of FOXO transcription factor DAF-16 that regulates expression of stress-resistant genes. Here we isolate a new gene called daf-31; this gene encodes a protein that regulates C. elegans larval development, metabolism and adult lifespan. This protein has been found in other species to be part of an enzyme that functions to modify other proteins. We show that overexpression of our newly discovered protein stimulates the transcriptional activity of DAF-16. Interestingly, abnormal regulation of human proteins similar to DAF-31 results in tumor formation. It is known that human FOXO proteins prevent tumorigenesis. Therefore, it is possible that abnormal DAF-31 activity may lead to tumor growth by reducing DAF-16 activity. Thus, the present study may not only contribute to understanding the role of a universal enzyme in controlling development, metabolism and lifespan in other organisms besides worms but may also shed light on the mechanisms of tumorigenesis in humans.
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影响因子：
11.8
作者：
Gerisch, B;Weitzel, C;Antebi, A
通讯作者：
Antebi, A
影响因子：
12.3
作者：
通讯作者：
--
影响因子：
4.8
作者：
Honda, Y;Honda, S
通讯作者：
Honda, S
影响因子：
64.5
作者：
Apfeld, J;Kenyon, C
通讯作者：
Kenyon, C
DOI：
10.1073/pnas.0901931106
发表时间：
2009-05-19
影响因子：
11.1
作者：
Arnesen, Thomas;Van Damme, Petra;Gevaert, Kris
通讯作者：
Gevaert, Kris