Protein Phosphatase 1 and Its Complexes in Carcinogenesis
Joao Figueiredo, Odete A. B. da Cruz e Silva and Margarida Fardilha
Affiliation: Centro de Biologia Celular, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
Keywords: Cancer therapy, phosphatase, PPP1, PPP1 interacting proteins, signaling pathways in cancer.
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.
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