Global analysis of cancer stem cell-specific phosphorylation of basic amino acids for application to cancer treatment

碱性氨基酸的磷酸化是一个古老的知识；然而，从他们明显的不稳定性来看，这一点几乎没有得到检验。我们发现游离磷酸化的碱性氨基酸在干细胞富集的癌症人群中增加。特别是磷酸甘氨酸抑制丙酮酸激酶活性，诱导有氧糖酵解。抑制有氧糖酵解和诱导氧化磷酸化可降低癌细胞的干性。因此，磷酸甘氨酸可能与癌症干细胞的能量产生和干细胞维持有关。我们还研究了组蛋白赖氨酸残基磷酸化对表观遗传学的影响。组蛋白赖氨酸磷酸化对赖氨酸残基的乙酰化或甲基化没有简单的抑制作用。组蛋白赖氨酸磷酸化可诱导赖氨酸残基向乙酰化或甲基化过渡。

Phosphorylation of basic amino acids were an old knowledge; however, it was hardly examined from their marked lability. We found the free phosphorylated basic amino acids were increased in stem cell-enriched cancer population. Especially, phosphoarginine inhibited pyruvate kinase activity, which induced aerobic glycolysis. Inhibition of the aerobic glycolysis and induction of oxidative phosphorylation decreased stemness of cancer cells. Thus, phosphoarginine might be associated with the energy production of cancer stem cells and stemness maintenance. We also examined the effect of phosphorylation of histone lysine residue on the epigenetics. Histone lysine phosphorylation did not show a simple inhibition of acetylation or methylation of the lysine residue. Histone lysine phosphorylation might induce a transitional status to acetylation or methylation of the lysine residue.