磷酸果糖激酶 1 糖基化调节细胞生长和代谢。
Phosphofructokinase 1 glycosylation regulates cell growth and metabolism.
机构信息
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
出版信息
Science. 2012 Aug 24;337(6097):975-80. doi: 10.1126/science.1222278.
Abstract
Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention.
摘要
癌细胞必须在不断变化的微环境中满足快速细胞生长的代谢需求。我们证明了蛋白质的 O-连接β-N-乙酰氨基葡萄糖（O-GlcNAcylation）的动态翻译后修饰是葡萄糖代谢的关键代谢调节剂。磷酸果糖激酶 1（PFK1）丝氨酸 529 的 O-GlcNAcylation 是对缺氧的反应诱导的。糖基化抑制了 PFK1 的活性，并将葡萄糖通量重新引导通过戊糖磷酸途径，从而为癌细胞赋予了选择性生长优势。阻断 PFK1 丝氨酸 529 的糖基化可减少体外癌细胞增殖并损害体内肿瘤形成。这些研究揭示了癌症中代谢途径调节的一个以前未被描述的机制，以及治疗干预的一个可能靶点。
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