TY - JOUR
T1 - Evidence for phosphatase activity of p27SJ and its impact on the cell cycle
AU - Darbinian, Nune
AU - Czernik, Marta
AU - Darbinyan, Armine
AU - Elias, Mikael
AU - Chabriere, Eric
AU - Bonasu, Surekha
AU - Khalili, Kamel
AU - Amini, Shohreh
PY - 2009/6/1
Y1 - 2009/6/1
N2 - 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.
AB - 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.
KW - Ding family
KW - Phosphatase activity
KW - p27SJ
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U2 - 10.1002/jcb.22135
DO - 10.1002/jcb.22135
M3 - Article
C2 - 19343785
AN - SCOPUS:66749162131
VL - 107
SP - 400
EP - 407
JO - Journal of supramolecular structure and cellular biochemistry
JF - Journal of supramolecular structure and cellular biochemistry
SN - 0730-2312
IS - 3
ER -