Centro de Biologia Celular, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
Curr Cancer Drug Targets. 2014;14(1):2-29. doi: 10.2174/15680096113136660106.
Understanding the molecular mechanisms and the signaling pathways that underlie the pathology of cancer progression is crucial for the development of novel diagnostic and therapeutic tools. A major common mechanism used by cells to regulate intracellular signal transduction pathways is reversible protein phosphorylation which results in profound changes in cellular responses. This mechanism relies on the coordinated action of two families of proteins: protein kinases and protein phosphatases. Interestingly, there are 3 to 5 times fewer phosphatases than kinases, suggesting that the specificity of substrates is not only due to the variety of the catalytic subunits but also to the diversity of the regulatory subunits. This is particularly true for PhosphoProtein Phosphatase 1 (PPP1) for which more than 200 PPP1 Interacting Proteins (PIPs) have thus far been identified. PIPs can act as targeting subunits, substrates and activity regulators. Many PPP1/PIPs complexes are involved in signaling pathways that regulate cellular growth, cell cycle and apoptosis; processes known to be deregulated in cancer. This review will describe the cellular pathways, many of which involve PPP1/PIP complexes, that when deregulated lead to cancer. Furthermore, the possibility of PPP1/PIP complexes being considered novel targets to cancer diagnostic and therapy will be addressed.
了解癌症进展病理学的分子机制和信号通路对于开发新的诊断和治疗工具至关重要。细胞用来调节细胞内信号转导途径的一种主要共同机制是可逆蛋白质磷酸化，这导致细胞反应发生深刻变化。该机制依赖于两类蛋白质的协调作用：蛋白激酶和蛋白磷酸酶。有趣的是，磷酸酶的数量比激酶少 3 到 5 倍，这表明底物的特异性不仅取决于催化亚基的多样性，还取决于调节亚基的多样性。对于磷酸化蛋白磷酸酶 1（PPP1）来说尤其如此，迄今为止已经鉴定出超过 200 种 PPP1 相互作用蛋白（PIP）。PIP 可以作为靶向亚基、底物和活性调节剂。许多 PPP1/PIP 复合物参与调节细胞生长、细胞周期和细胞凋亡的信号通路；这些过程在癌症中已知被失调。本综述将描述涉及 PPP1/PIP 复合物的细胞途径，其中许多途径在失调时导致癌症。此外，还将探讨 PPP1/PIP 复合物是否可以被视为癌症诊断和治疗的新靶点。
