TAp73 promotes anabolism.
TAp73 promotes anabolism.
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DOI：
10.18632/oncotarget.2667
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发表时间：
2014-12-30
期刊：
影响因子：
--
通讯作者：
Rufini A
中科院分区：
文献类型：
--
作者：
Amelio I;Antonov AA;Catani MV;Massoud R;Bernassola F;Knight RA;Melino G;Rufini A
代谢适应已成为癌症的标志和有前途的治疗靶点，因为快速增殖的癌细胞适应其代谢，增加营养摄取并重组代谢通量以支持生物合成。转录因子p73属于p53家族，通过其两个N-末端亚型调节肿瘤发生，具有（TAp 73）或不具有（Δ Np 73）反式激活结构域。TAp 73至少部分通过诱导细胞周期停滞和细胞凋亡以及通过调节基因组稳定性来充当肿瘤抑制因子。在这里，我们试图研究TAp 73是否也影响癌细胞的代谢谱。利用高通量代谢组学，我们揭示了TAp 73在促进瓦尔堡效应和细胞代谢中的彻底和意想不到的作用。表达TAp 73的细胞显示糖酵解速率增加、氨基酸摄取增加以及乙酰辅酶A的水平和生物合成增加。此外，我们报告了广泛的TAp 73介导的上调几个合成代谢途径，包括多胺和膜磷脂的合成。TAp 73表达还增加细胞甲基供体S-腺苷甲硫氨酸（SAM），可能影响甲基化和表观遗传学，并促进精氨酸代谢，提示在细胞外基质（ECM）建模中的作用。总之，我们的数据表明，TAp 73调节多种代谢途径，这些代谢途径影响许多细胞功能，但总体而言，这些代谢途径会聚在一起以维持细胞生长和增殖。
Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
4.3
作者：
Chillemi, Giovanni;Davidovich, Pavel;Melino, Gerry
通讯作者：
Melino, Gerry
影响因子：
4.3
作者：
Bennetzen, Martin V.;Larsen, Dorthe Helena;Andersen, Jens S.
通讯作者：
Andersen, Jens S.
DOI：
10.1083/jcb.200709049
发表时间：
2008-06-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen K;Kirber MT;Xiao H;Yang Y;Keaney JF Jr
通讯作者：
Keaney JF Jr
影响因子：
29
作者：
Berkers CR;Maddocks OD;Cheung EC;Mor I;Vousden KH
通讯作者：
Vousden KH