美国纪念斯隆-凯特琳癌症研究中心Craig B. Thompson研究团队发现，当细胞外半胱氨酸受限时，转硫作用的活性可以支持细胞生长。相关论文2019年10月10日在线发表在《细胞—代谢》杂志上。

研究人员探究了细胞外半胱氨酸受限后转硫作用的调控及其在维持细胞增殖中的作用。据报道，随着人类肿瘤大小的增长，这种情况会发生在人类肿瘤中。研究人员观察到一部分癌细胞系中的转硫酶的组成性表达，而在其他细胞中，这些酶是在半胱氨酸剥夺后被诱导的。研究人员发现固有的和诱导的转硫活动都有助于细胞半胱氨酸池和氧化还原稳态。转硫速率取决于细胞进行甲基化反应的能力，其将S-腺苷甲硫氨酸转化为S-腺苷高半胱氨酸。

最后，这些结果表明，转硫介导的半胱氨酸合成对于促进体内肿瘤生长至关重要。

据介绍，半胱氨酸既充当蛋白质翻译的构建单元，又作为谷胱甘肽合成的限制性底物，从而维持细胞的抗氧化剂系统。除了转运蛋白介导的摄取外，还可以通过转硫途径由蛋氨酸合成细胞半胱氨酸。

附：英文原文

Title: Transsulfuration Activity Can Support Cell Growth upon Extracellular Cysteine Limitation

Author: Jiajun Zhu, Mirela Berisa, Simon Schwrer, Weige Qin, Justin R. Cross, Craig B. Thompson

Issue&Volume: 10 October 2019

Abstract: 

Cysteine acts both as a building unit for protein translation and as the limiting substrate for glutathione synthesis to support the cellular antioxidant system. In addition to transporter-mediated uptake, cellular cysteine can also be synthesized from methionine through the transsulfuration pathway. Here, we investigate the regulation of transsulfuration and its role in sustaining cell proliferation upon extracellular cysteine limitation, a condition reported to occur in human tumors as they grow in size. We observed constitutive expression of transsulfuration enzymes in a subset of cancer cell lines, while in other cells, these enzymes are induced following cysteine deprivation. We show that both constitutive and inducible transsulfuration activities contribute to the cellular cysteine pool and redox homeostasis. The rate of transsulfuration is determined by the cellular capacity to conduct methylation reactions that convert S-adenosylmethionine to S-adenosylhomocysteine. Finally, our results demonstrate that transsulfuration-mediated cysteine synthesis is critical in promoting tumor growth in vivo.

DOI: 10.1016/j.cmet.2019.09.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30512-1