A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism
A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism
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DOI：
10.1128/mcb.22.16.5793-5800.2002
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发表时间：
2002-08-01
影响因子：
5.3
通讯作者：
Cole, MD
中科院分区：
文献类型：
--
作者：
Nikiforov, MA;Chandriani, S;Cole, MD
将富含Myc应答cDNA但耗尽myc cDNAs的cDNA文库用于c-myc缺失细胞中生长增强的功能性筛选。线粒体丝氨酸羟甲基转移酶（mSHMT），能够部分互补的c-myc-null细胞的生长缺陷的cDNA克隆进行了鉴定。表达分析和染色质免疫沉淀证实mSHMT是Myc的直接靶基因。此外，编码相同酶的细胞质同种型的单独基因也是Myc调控的直接靶点。SHMT酶是叶酸代谢以及核苷酸和氨基酸生物合成所需的一碳单元的主要来源。我们的数据建立了Myc和细胞代谢调节之间的新功能联系。
A cDNA library enriched with Myc-responsive cDNAs but depleted of myc cDNAs was used in a functional screen for growth enhancement in c-myc-null cells. A cDNA clone for mitochondrial serine hydroxymethyltransferase (mSHMT) that was capable of partial complementation of the growth defects of c-myc-null cells was identified. Expression analysis and chromatin immunoprecipitation demonstrated that mSHMT is a direct Myc target gene. Furthermore, a separate gene encoding the cytoplasmic isoform of the same enzyme is also a direct target of Myc regulation. SHMT enzymes are the major source of the one-carbon unit required for folate metabolism and for the biosynthesis of nucleotides and amino acids. Our data establish a novel functional link between Myc and the regulation of cellular metabolism.