Evidence for phosphatase activity of p27SJ and its impact on the cell cycle |
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Authors: | Nune Darbinian Marta Czernik Armine Darbinyan Mikael Elias Eric Chabriere Surekha Bonasu Kamel Khalili Shohreh Amini |
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Institution: | 1. Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122;2. Architecture et Fonction de Macromolécules Biologiques, CNRS‐Université de la Méditerranée, 13288 Marseille, France;3. Department of Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122 |
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Abstract: | p27SJ, a novel protein isolated from St John's wort (Hypericum perforatum), belongs to an emerging family of DING proteins that are related to a prokaryotic phosphate‐binding protein superfamily. Here we demonstrate that p27SJ exhibits phosphatase activity and that its expression in cells decreases the level of phosphorylated Erk1/2, a key protein of several signaling pathways. Treatment of p27SJ‐expressing cells with phosphatase inhibitors including okadaic acid, maintained Erk1/2 in its phosphorylated form, suggesting that dephosphorylation of Erk1/2 is mediated by p27SJ. Further, expression of p27SJ affects Erk1/2 downstream regulatory targets such as STAT3 and CREB. Moreover, the level of expression of cyclin A that associates with active ERK1/2 and is regulated by CREB, was modestly reduced in p27SJ‐expressing cells. Accordingly, results from in vitro kinase assays revealed a noticeable decrease in the activity of cyclin A in cells expressing p27SJ. Cell cycle analysis demonstrated dysregulation at S and G2/M phases in cells expressing p27SJ, supporting the notion that a decline in cyclin A activity by p27SJ has a biological impact on cell growth. These observations provide evidence that p27SJ alters the state of Erk1/2 phosphorylation, and impacts several biological events associated with cell growth and function. J. Cell. Biochem. 107: 400–407, 2009. © 2009 Wiley‐Liss, Inc. |
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Keywords: | DING family phosphatase activity p27SJ |
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