Korrodi-Gregório Luís, Silva Joana Vieira, Santos-Sousa Luís, Freitas Maria João, Felgueiras Juliana, Fardilha Margarida
Signal Transduction Laboratory, Centre for Cell Biology, Biology Department, Health Sciences Department, University of Aveiro, Aveiro, Portugal.
J Cell Mol Med. 2014 Apr;18(4):555-67. doi: 10.1111/jcmm.12266. Epub 2014 Mar 15.
Protein phosphorylation is a key mechanism by which normal and cancer cells regulate their main transduction pathways. Protein kinases and phosphatases are precisely orchestrated to achieve the (de)phosphorylation of candidate proteins. Indeed, cellular health is dependent on the fine-tune of phosphorylation systems, which when deregulated lead to cancer. Transforming growth factor beta (TGF-β) pathway involvement in the genesis of prostate cancer has long been established. Many of its members were shown to be hypo- or hyperphosphorylated during the process of malignancy. A major phosphatase that is responsible for the vast majority of the serine/threonine dephosphorylation is the phosphoprotein phosphatase 1 (PPP1). PPP1 has been associated with the dephosphorylation of several proteins involved in the TGF-β cascade. This review will discuss the role of PPP1 in the regulation of several TGF-β signalling members and how the subversion of this pathway is related to prostate cancer development. Furthermore, current challenges on the protein phosphatases field as new targets to cancer therapy will be addressed.
蛋白质磷酸化是正常细胞和癌细胞调节其主要转导途径的关键机制。蛋白激酶和磷酸酶被精确调控，以实现候选蛋白的（去）磷酸化。事实上，细胞健康依赖于磷酸化系统的微调，该系统失调会导致癌症。转化生长因子β（TGF-β）途径参与前列腺癌的发生早已得到证实。在恶性肿瘤发生过程中，其许多成员被证明存在磷酸化不足或过度磷酸化的情况。负责绝大多数丝氨酸/苏氨酸去磷酸化的主要磷酸酶是蛋白磷酸酶1（PPP1）。PPP1与TGF-β级联反应中几种蛋白质的去磷酸化有关。本综述将讨论PPP1在调节几种TGF-β信号成员中的作用，以及该途径的颠覆与前列腺癌发展的关系。此外，还将探讨蛋白质磷酸酶领域作为癌症治疗新靶点目前所面临的挑战。
