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| Content Provider | PubMed Central |
|---|---|
| Author | Xu, Dong Song, Renduo Wang, Guohui Jeyabal, Prince V. S. Weiskoff, Amanda M. Ding, Kefeng Shi, Zheng-zheng |
| Copyright Year | 2016 |
| Abstract | OLA1 is an Obg family P-loop NTPase that possesses both GTP- and ATP-hydrolyzing activities. Here we report that OLA1 is a GSK3β interacting protein, and through its ATPase activity, inhibits the GSK3β-mediated activation of protein serine/threonine phosphatase 1 (PP1). It is hypothesized that GSK3β phosphorylates inhibitor 2 (I-2) of PP1 at Thr-72 and activates the PP1 · I-2 complex, which in turn dephosphorylates and stimulates GSK3β, thus forming a positive feedback loop. We revealed that the positive feedback loop is normally suppressed by OLA1, and becomes over-activated under OLA1 deficiency, resulting in increased cellular PP1 activity and dephosphorylation of multiple Ser/Thr phosphoproteins, and more strikingly, decreased global protein threonine phosphorylation. Furthermore, using xenograft models of colon cancer (H116) and ovarian cancer (SKOV3), we established a correlation among downregulation of OLA1, over-activation of the positive feedback loop as indicated by under-phosphorylation of I-2, and more aggressive tumor growth. This study provides the first evidence for the existence of a GSK3β-I-2-PP1 positive feedback loop in human cancer cells, and identifies OLA1 as an endogenous suppressor of this signaling motif. |
| Related Links | http://dx.doi.org/10.18632/oncotarget.6496 |
| Starting Page | 3427 |
| File Format | |
| ISSN | 19492553 |
| e-ISSN | 19492553 |
| Journal | Oncotarget |
| Issue Number | 3 |
| Volume Number | 7 |
| Language | English |
| Publisher | Impact Journals LLC |
| Publisher Date | 2016-01-01 |
| Access Restriction | Open |
| Rights Holder | Impact Journals LLC |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |
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