p38 Mitogen-activated protein kinase pathway suppresses cell survival by inducing dephosphorylation of mitogen-activated protein/extracellular signal-regulated kinase kinase1,2
Authors: Jukka Westermarck
Veli-Matti Kähäri
Jiahuai Han
Melissa R Junttila
Song-Ping Li
Journal: Cancer research (2003)
Discipline: CLINICAL MEDICINE
Keywords: Raf; MEK; p38; apoptosis; survival signaling
Affiliations: Turku Centre for Biotechnology, University of Turku, Finland.

Abstract:  Raf/mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)1,2/extracellular signal-regulated kinase1,2 and MKK3,6/p38 mitogen-activated protein kinase pathways play an important role in cellular survival and apoptosis. The results of this study identify novel mechanisms to explain the opposing effects of these pathways in the regulation of apoptosis induction. Our results show that activation of p38 by adenoviral expression of MKK3b or arsenite treatment was followed by rapid dephosphorylation of MEK1,2 and subsequent apoptosis in human skin fibroblasts. Inhibition of p38 activity by SB203580 and adenoviral expression of dominant-negative forms of p38 potently inhibited MEK1,2 dephosphorylation and apoptosis. Strikingly, p38-mediated dephosphorylation of MEK1,2, was not detected in a series of transformed human cell lines. Taken together, we provide evidence for mechanisms unidentified previously that negatively regulates survival signaling during apoptosis induction. In addition, we show that in all transformed cell lines we have studied thus far, the function of this pathway is impaired. 

Retracted: No

PubPeer comments:
 Erratum The following was originally published in Volume 25, No. 6, pages 967u2013974, 2017 (doi: https: doi.org 10.3727 096504016X14803476672380). Because it was recently revealed that the testing reagent supplier used had some inferior products, we wanted to repeat the testing and check the reliability of the data. As a result, some of the expression levels were revealed to be different from the experimental results, which affected some of the display in the figures. Therefore, corrected versions of **Figures 1, 2, 3, and 4** are provided here. The figures have also been replaced with the corrected versions in the original published version in the online site . These corrections do not affect the conclusion of the original article. , 
 Fig 2C.  miR-107 promotes the survival of human CRC cells. SW480 and LoVo cells were transfected by the miR-107 inhibitor, mimic, or negative miRNA (C-MiR). ... (C) Flow cytometric analysis was performed to evaluate the apoptosis rate of transfected cells . ![file] Can the authors comment on the appearance of the same flow-cytometry plots as Fig 2B from [Meng et al (2017)] , albeit from different cell-lines under different conditions, with slightly different quadrant percentages? ![] And in Fig 2C from [Li et al (2016)] ? ![] Fig 2B from [Wang et al (2017)] ? ![] , 
 Fig 2.  miR-107 promotes the survival of human CRC cells. SW480 and LoVo cells were transfected by the miR-107 inhibitor, mimic, or negative miRNA (C-MiR). ![file] Fig 2 from [Lu et al (2017)] .  miR-17-3P promotes the survival of human colorectal cancer cells. SW480 and LoVo cells were transfected by miR-17-3P inhibitor, mimic or negative miRNA (C-MiR) ![file] Two papers report identical results, except for the miRNA. , 
 SimText comparison of the Discussion sections: ![file] , 
 Abstract:  In addition, we identified prostate apoptosis response-4 (Par4) as a direct target of miR-107 with a potential binding site on the 3u00a2-UTR of mRNA, as evaluated by **bioinformatics prediction** and luciferase reporter assay. Discussion:  By **online bioinformatic prediction** and luciferase reporter assay, we confirmed that there is a binding site of miR-107 in the 3u00a2-UTR of Par4 mRNA, and Par4 is a direct target of miR-107 in human CRC cells . This seems to allude to a paragraph of Results:  **Par4 Is the Target of miR-107** Par4 is a tumor suppressor in various cancers, including human CRC15. We predicted the potential targets of miR-107 using Microrna.org and TargetScan databases and found that there is a possible binding site of miR-107 in the 3u2032-UTR of Par4 mRNA (Fig. 3A). To identify the prediction and elucidate the underlying mechanism by which miR-107 regulates CRC cell survival, we conducted the luciferase reporter assay in SW480 and LoVo cells. The wild or mutant 3u2032-UTR of Par4 mRNA was cloned into the luciferase vector (Fig. 3A). The luciferase activity of wild Par4-3u2032UTR was strongly reduced by the miR-107 mimic, but there was no difference in the luciferase activity of mutant Par4-3u2032UTR in CRC cells (Fig. 3B). ![file] Lu et al (2017) have the same paragraph:  **Par4 is the target of miR-17-3P** Par4 is a tumor suppressor in various cancers, including human CRC (11). We predicated the potential targets of miR-17-3P using miRDB and TargetScan databases, and found that there is possible binding site of miR-17-3P on 3u2032-UTR of Par4 (Fig. 3A). To identify the prediction and elucidate the underlying mechanism by which miR-17-3P regulates CRC cells survival, we conducted the luciferase reporter assay in SW480 and LoVo cells. As seen in Fig. 3A, the wild or mutant 3u2032-UTR of Par4 were cloned into luciferase vector, respectively. Luciferase activities of wild Par4-3u2032UTR were strongly reduced by miR-17-3P mimic, but there was no difference in the luciferase activities of mutant Par4-3u2032UTR in CRC cells (Fig. 3B). ![file] , 
 Here I have compared the two References sections, as another reminder that the same paper has been published twice with very little alteration. ![file] Other products of a papermill specialising in this style of paper are collated in a spreadsheet: https: docs.google.com spreadsheets d 19wUtpXazLg2zKbTpDBuq0smG6-A7VHYifkieoyyuTcQ edit?usp=sharing ,