Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1α.
Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1α.
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DOI：
10.1101/gad.309062.117
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发表时间：
2018-02-01
影响因子：
10.5
通讯作者：
Murphy ME
中科院分区：
文献类型：
--
作者：
Basu S;Gnanapradeepan K;Barnoud T;Kung CP;Tavecchio M;Scott J;Watters A;Chen Q;Kossenkov AV;Murphy ME
Basu等人表明突变型p53通过结合和调节PGC-1α的能力增强肿瘤的迁移和转移，并且这种调节明显受到密码子72多态性的影响。p53蛋白的突变形式通常具有促肿瘤发生功能，通过其“功能获得”活性赋予肿瘤细胞增加的存活和迁移。TP 53第72位氨基酸（Pro72 Arg;在此称为P72和R72）的常见多态性是否以及如何影响这种功能的获得尚未确定。我们发现突变型p53通过结合和调节PGC-1α的能力增强肿瘤的迁移和转移，并且这种调节明显受到密码子72多态性的影响。具有突变型p53的R72变体的肿瘤细胞显示PGC-1α功能增加沿着线粒体功能和转移能力大大增加。与P72相比，含有突变型p53和R72变体的乳腺癌显示较差的预后。综合结果显示PGC-1α是突变型p53的一种新的“功能获得性”伴侣，并表明密码子72多态性影响突变型p53对代谢和转移的影响。
Basu et al. show that mutant p53 enhances migration and metastasis of tumors through the ability to bind and regulate PGC-1α and that this regulation is markedly impacted by the codon 72 polymorphism. Mutant forms of p53 protein often possess protumorigenic functions, conferring increased survival and migration to tumor cells via their “gain-of-function” activity. Whether and how a common polymorphism in TP53 at amino acid 72 (Pro72Arg; referred to here as P72 and R72) impacts this gain of function has not been determined. We show that mutant p53 enhances migration and metastasis of tumors through the ability to bind and regulate PGC-1α and that this regulation is markedly impacted by the codon 72 polymorphism. Tumor cells with the R72 variant of mutant p53 show increased PGC-1α function along with greatly increased mitochondrial function and metastatic capability. Breast cancers containing mutant p53 and the R72 variant show poorer prognosis compared with P72. The combined results reveal PGC-1α as a novel “gain-of-function” partner of mutant p53 and indicate that the codon 72 polymorphism influences the impact of mutant p53 on metabolism and metastasis.
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影响因子：
30.8
作者：
Dumont, P;Leu, JIJ;Murphy, M
通讯作者：
Murphy, M
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
8.8
作者：
Kung CP;Leu JI;Basu S;Khaku S;Anokye-Danso F;Liu Q;George DL;Ahima RS;Murphy ME
通讯作者：
Murphy ME
DOI：
10.1083/jcb.201009059
发表时间：
2011-01-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Muller PA;Vousden KH;Norman JC
通讯作者：
Norman JC
影响因子：
3.8
作者：
Bonfigli, Anna Rita;Sirolla, Cristina;Franceschi, Claudio
通讯作者：
Franceschi, Claudio