Gizak Agnieszka, Budziak Bartosz, Domaradzka Aleksandra, Pietras Łukasz, Rakus Dariusz
Department of Molecular Physiology and Neurobiology, University of Wrocław, Sienkiewicza 21, 50-335, Wrocław, Poland.
Department of Molecular Physiology and Neurobiology, University of Wrocław, Sienkiewicza 21, 50-335, Wrocław, Poland.
Adv Biol Regul. 2025 Jan;95:101057. doi: 10.1016/j.jbior.2024.101057. Epub 2024 Oct 23.
Fructose 1,6-bisphosphatase (FBP) is a regulatory enzyme of gluconeogenesis that also influences in a non-catalytic manner - via protein-protein interactions - cell cycle-dependent events, mitochondria biogenesis and polarization, synaptic plasticity and even cancer progression. FBP reduces glycolytic capacity of cells via blocking HIF-1α transcriptional activity and modulating NF-κB action, and influences oxidative metabolism by binding to c-MYC. Because FBP limits the energy-producing potential of cells and because a reduction of FBP amounts is observed in cancer cells, FBP is considered to be an anti-oncogenic protein. This is supported by the observation that cancer cells overexpress aldolase A (ALDOA), a pro-oncogenic protein that can bind to FBP and potentially block its anti-oncogenic activity. Interestingly, only the muscle isozyme of FBP (FBP2) interacts strongly with ALDOA, whereas the binding of the liver isozyme (FBP1) to ALDOA is more than an order of magnitude weaker. Here, we briefly review the most important evidence supporting the anti-oncogenic function of FBP and discuss what structural properties of the two FBP isozymes allow FBP2, rather than FBP1, to exert more flexible anticancer functions.
果糖1,6 - 二磷酸酶（FBP）是糖异生的一种调节酶，它还通过蛋白质 - 蛋白质相互作用以非催化方式影响细胞周期依赖性事件、线粒体生物发生和极化、突触可塑性甚至癌症进展。FBP通过阻断缺氧诱导因子-1α（HIF - 1α）的转录活性和调节核因子κB（NF - κB）的作用来降低细胞的糖酵解能力，并通过与c - MYC结合影响氧化代谢。由于FBP限制了细胞产生能量的潜力，并且在癌细胞中观察到FBP含量降低，因此FBP被认为是一种抗癌蛋白。癌细胞过表达醛缩酶A（ALDOA），这是一种促癌蛋白，它可以与FBP结合并可能阻断其抗癌活性，这一观察结果支持了上述观点。有趣的是，只有FBP的肌肉同工酶（FBP2）与ALDOA强烈相互作用，而肝脏同工酶（FBP1）与ALDOA的结合力则弱一个数量级以上。在此，我们简要回顾支持FBP抗癌功能的最重要证据，并讨论两种FBP同工酶的哪些结构特性使FBP2而非FBP1能够发挥更灵活的抗癌功能。
