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Title: Phosphoprotein phosphatase 1 isoforms alpha and gamma respond differently to prodigiosin treatment and present alternative kinase targets in melanoma cells
Author: Fardilha, Margarida
Figueiredo, João
Espona Fiedler, Margarita
Felgueiras, Juliana
Korrodi-Gregório, Luís
Esteves, Sara L. C.
Rebelo, Sandra
Cruz e Silva, Odete A. B. da
Cruz e Silva, Edgar F. da
Pérez Tomás, Ricardo E.
Keywords: Proteïnes supressores de tumors
Regulació genètica
Tumor suppressor protein
Genetic regulation
Issue Date: 12-May-2014
Publisher: Scientific Research Publishing
Abstract: Reversible protein phosphorylation is a central regulatory mechanism of cell function. Deregulation of the balanced actions of protein kinases and phosphatases has been frequently associated with several pathological conditions, including cancer. Many studies have already addressed the role of protein kinases misregulation in cancer. However, much less is known about protein phosphatases influence. Phosphoprotein Phosphatase 1 (PPP1) is one of the major serine/threonine protein phosphatases who has three catalytic isoforms: PPP1CA, PPP1CB, and PPP1CC. Its function is achieved by binding to regulatory subunits, known as PPP1-interacting proteins (PIPs), which may prefer a catalytic isoform. Also, some inhibitors/enhancers may exhibit isoform specificity. Here we show that, prodigiosin (PG), a molecule with anticancer properties, promotes the formation of PPP1CA-AKT complex and not of PPP1CC-MAPK complex. Both, AKT and MAPK, are well-known PIPs from two pathways that crosstalk and regulate melanoma cells survival. In addition, the analysis performed using surface plasmon resonance (SPR) technology indicates that PPP1 interacts with obatoclax (OBX), a drug that belongs to the same family of PG. Overall, these results suggest that PG might, at least in part, act through PPP1C/PIPs. Also, this study is pioneer in demonstrating PPP1 isoform-specific modulation by small molecules.
Note: Reproducció del document publicat a:
It is part of: Journal of Biophysical Chemistry, 2014, vol. 5, num. 2, p. 67-77
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ISSN: 2153-036X
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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