title: Protein phosphatase 1 and its complexes in carcinogenesis.
abstract: 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.
authors.forename: Joao
authors.initials: J
authors.lastname: Figueiredo
authors.forename: Odete A B
authors.initials: OA
authors.lastname: da Cruz E Silva
authors.affiliation: Centro de Biologia Celular, Universidade de Aveiro, 3810-193 Aveiro, Portugal. mfardilha@ua.pt.
authors.forename: Margarida
authors.initials: M
authors.lastname: Fardilha
mesh_terms: D053477:Apoptotic Protease-Activating Factor 1 / Q000737:chemistry / Q000378:metabolism; D019313:BRCA1 Protein / Q000378:metabolism; D001665:Binding Sites; D063646:Carcinogenesis / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D020134:Catalytic Domain; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051057:Proto-Oncogene Proteins c-akt; C517187:PPP1CA protein, human; D054645:Protein Phosphatase 1; D020169:Caspases