Protein Phosphatase 1 and Its Complexes in Carcinogenesis

Joao      Figueiredo; Odete   A. B.   da Cruz e Silva; Margarida      Fardilha

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.

Keywords: Cancer therapy, phosphatase, PPP1, PPP1 interacting proteins, signaling pathways in cancer.

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