To be, or not to be: functional dilemma of p53 metabolic regulation.
To be, or not to be: functional dilemma of p53 metabolic regulation.
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DOI：
10.1097/cco.0000000000000024
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发表时间：
2014-01
影响因子：
3.4
通讯作者：
Gu W
中科院分区：
文献类型：
--
作者：
Wang SJ;Gu W
近年来，p53 在代谢调节中的新兴作用引起了人们极大的兴趣。虽然 p53 的凋亡和生长停滞功能仍然是保持基因组稳定性的重要机制，但 p53 的代谢功能在促进 p53 介导的肿瘤抑制方面显示出越来越大的潜力。去年的大量研究为 p53 的代谢功能及其在肿瘤发生中的影响提供了进一步的见解。这些发现阐明了 p53 代谢调节在肿瘤生物学中的重要性。已经确定了几个新的 p53 代谢靶标，它们涉及代谢的各个方面。此外，虽然一些研究证明了 p53 代谢基因的潜在肿瘤抑制功能，但其他研究则揭示了这些靶标在肿瘤和正常细胞中的促生存作用。具体来说，TIGAR被认为可以通过代谢微调来促进肿瘤抑制，但事实上，TIGAR缺陷的小鼠表现出肿瘤发生的减少。最后，3KR 小鼠模型的表征强调了 p53 代谢调节在肿瘤抑制中的重要性，同时也暗示了选择性调节 p53 代谢靶点的潜在机制。最近的证据强调了 p53 代谢功能的日益复杂性。许多p53代谢基因的表达会引起抗肿瘤和致瘤作用，这表明p53实际上可能有助于细胞保护和肿瘤抑制。未来的研究必须仔细剖析 p53 代谢功能的二元性，更好地了解 p53 如何调节代谢靶点可能有助于设计癌症疗法。
In recent years, the emerging role of p53 in metabolic regulation has been a topic of great interest. While apoptotic and growth arrest functions of p53 remain as important mechanisms for preserving genomic stability, metabolic functions of p53 show increasing potential in contributing to p53-mediated tumor suppression. Numerous studies in the past year provided further insights on the metabolic functions of p53 and their implications in tumorigenesis. These findings illuminate the significance of p53 metabolic regulation in tumor biology. Several novel p53 metabolic targets have been identified that are involved in various aspects of metabolism. Furthermore, while some studies demonstrate the potential tumor suppressive function of p53 metabolic genes, others reveal the pro-survival role of those targets in both tumor and normal cells. Specifically, TIGAR has been thought to promote tumor suppression through metabolic fine-tuning, yet TIGAR-deficient mice, in fact, display reduction in tumorigenesis. Finally, characterization of the 3KR mouse model underscored the significance of p53 metabolic regulation in tumor suppression, while also alluding to the potential mechanism for selective regulation of p53 metabolic targets. Recent evidence highlighted the ever-growing complexity of p53 metabolic functions. Expression of many p53 metabolic genes elicits both anti-tumor and tumorigenic effects, suggesting that p53 may in fact contribute to cellular protection as well as tumor suppression. Future studies must carefully dissect the duality of p53 metabolic function, and greater understanding of how metabolic targets are regulated by p53 may prove useful in designing cancer therapies.