Over-expression of the constitutive AMPylase FIC-1(E274G) does not deplete cellular ATP pools in C. elegans.

Over-expression of the constitutive AMPylase FIC-1(E274G) does not deplete cellular ATP pools in C. elegans.
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DOI:
10.17912/micropub.biology.000409
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发表时间:
2021-06-25
影响因子:
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通讯作者:
Truttmann MC
Truttmann MC
中科院分区:
其他
文献类型:
--
作者:
Champion M;Truttmann MC

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蛋白质AMP化已成为一种翻译后蛋白质修饰,调节细胞蛋白质稳态。AMP化由Fic AMP酶赋予,其催化AMP以ATP为代价共价连接至靶蛋白。组成型活性Fic AMP酶的过表达是有毒的。在这里,我们测试了过度的Fic AMPylase活性可能耗尽细胞ATP库,导致细胞死亡的假设。我们发现,增加/减少Fic AMP酶活性仅改变细胞ATP浓度约15%。这表明高腺苷酸化介导的细胞死亡可能不是细胞ATP耗竭的结果。
Protein AMPylation has emerged as a posttranslational protein modification regulating cellular proteostasis. AMPylation is conferred by Fic AMPylases, which catalyze the covalent attachment of AMP to target proteins at the expense of ATP. Over-expression of constitutive-active Fic AMPylases is toxic. Here, we test the hypothesis that excessive Fic AMPylase activity could deplete cellular ATP pools, leading to cell death. We find that increased/decreased Fic AMPylase activity only alters cellular ATP concentrations by approximately 15%. This suggests that hyper-AMPylation-mediated cell death is likely not the consequence of cellular ATP depletion.