M2型丙酮酸激酶翻译后修饰在肿瘤发生和发展中的作用

Role in post-translational modification of M2-type pyruvate kinase in tumorigenesis and development

PKM2,即M2型丙酮酸激酶,因其在糖酵解中的关键作用及在多种肿瘤中的异常表达而备受关注。随着PKM2非代谢功能的发现,PKM2的丙酮酸激酶活性(在细胞质中以四聚体形式存在)和蛋白激酶活性(在细胞核中以二聚体形式存在)之间的切换再次使PKM2成为肿瘤研究的焦点。研究表明,PKM2是一种容易受多种翻译后修饰影响的蛋白质,而不同翻译后修饰对PKM2的细胞定位、结构及激酶活性转换等过程均具有重要的调节作用。PKM2多种翻译后修饰在肿瘤的发生和发展中发挥重要作用。如磷酸化及乙酰化修饰通过改变PKM2细胞定位促进核易位;糖基化、泛素化修饰通过影响PKM2结构转变促进其二聚体结构的形成;琥珀酰化及氧化还原修饰等通过影响激酶活性转变促进PKM2蛋白激酶活性的增强。无论是影响PKM2的结构还是转变细胞定位,都是通过改变其激酶活性来发挥促进或抑制肿瘤发展的作用。

PKM2,also known as M2-type pyruvate kinase,has attracted significant attention due to its crucial role in glycolysis and its abnormal expression in various tumors.With the discovery of PKM2’s non-metabolic functions,the transition between its pyruvate kinase activity(in the tetrameric form in the cytoplasm)and protein kinase activity(in the dimeric form in the nucleus)has once again made PKM2 a target of interest in cancer research.Studies have shown that PKM2 is a protein susceptible to various post-translational modifications,and different post-translational modifications play important regulatory roles in processes such as PKM2 cellular localization,structure,and enzyme activity conversion.In this review,we focused on the recent progress of multiple post-translational modifications of PKM2 and their important roles in tumor initiation and development.For example,phosphorylation and acetylation promote nuclear translocation by altering PKM2 cell localization;glycosylation and ubiquitination can promote the formation of dimer structure by affecting the structural transformation of PKM2;succinylation and redox modification promoted the enhancement of PKM2 kinase activity by affecting the transformation of kinase activity.Both changes affect the structure and cell localization of PKM2 and they play a role in promoting or inhibiting tumor development via altering its kinase activity.