title: Evidence for phosphatase activity of p27SJ and its impact on the cell cycle.
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.
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA.
authors.forename: Nune
authors.initials: N
authors.lastname: Darbinian
authors.forename: Marta
authors.initials: M
authors.lastname: Czernik
authors.forename: Armine
authors.initials: A
authors.lastname: Darbinyan
authors.forename: Mikael
authors.initials: M
authors.lastname: Elias
authors.forename: Eric
authors.initials: E
authors.lastname: Chabriere
authors.forename: Surekha
authors.initials: S
authors.lastname: Bonasu
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Shohreh
authors.initials: S
authors.lastname: Amini