The essential role of FKBP38 in regulating phosphatase of regenerating liver 3 (PRL-3) protein stability
The essential role of FKBP38 in regulating phosphatase of regenerating liver 3 (PRL-3) protein stability
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DOI：
10.1016/j.bbrc.2011.02.037
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发表时间：
2011-03-11
影响因子：
3.1
通讯作者：
Yoo, Ook-Joon
中科院分区：
文献类型：
--
作者：
Choi, Myung-Suk;Min, Sang-Hyun;Yoo, Ook-Joon
再生肝-3磷酸酶（PRL-3）是蛋白酪氨酸磷酸酶的一个成员，其失调与许多癌症的肿瘤发生和转移有关。然而，PRL-3调控的潜在机制尚不清楚。本研究利用酵母双杂交系统鉴定了肽基脯氨酸顺/反式异构酶fk506结合蛋白38 （FKBP38）为PRL-3的相互作用蛋白。FKBP38在体内特异性结合PRL-3，并且FKBP38的n端区域是与PRL-3结合的关键区域。FKBP38过表达会降低内源性PRL-3的表达水平，而siRNA对FKBP38的抑制会增加PRL-3蛋白的表达水平。此外，FKBP38通过蛋白-蛋白酶体途径促进内源性PRL-3蛋白的降解。此外，FKBP38抑制prl -3介导的p53活性和细胞增殖。这些结果表明，FKBP38是致癌蛋白PRL-3丰度的新调节剂，PRL-3稳定性的改变可以对细胞增殖产生巨大影响。因此，FKBP38可能在肿瘤发生中起关键作用。(C) 2011爱思唯尔公司版权所有。
The phosphatase of regenerating liver-3 (PRL-3) is a member of protein tyrosine phosphatases and whose deregulation is implicated in tumorigenesis and metastasis of many cancers. However, the underlying mechanism by which PRL-3 is regulated is not known. In this study, we identified the peptidyl prolyl cis/trans isomerase FK506-binding protein 38 (FKBP38) as an interacting protein of PRL-3 using a yeast two-hybrid system. FKBP38 specifically binds to PRL-3 in vivo, and that the N-terminal region of FKBP38 is crucial for binding with PRL-3. FKBP38 overexpression reduces endogenous PRL-3 expression levels, whereas the depletion of FKBP38 by siRNA increases the level of PRL-3 protein. Moreover, FKBP38 promotes degradation of endogenous PRL-3 protein via protein-proteasome pathway. Furthermore, FKBP38 suppresses PRL-3-mediated p53 activity and cell proliferation. These results demonstrate that FKBP38 is a novel regulator of the oncogenic protein PRL-3 abundance and that alteration in the stability of PRL-3 can have a dramatic impact on cell proliferation. Thus, FKBP38 may play a critical role in tumorigenesis. (C) 2011 Elsevier Inc. All rights reserved.