The dual-specificity phosphatase DUSP14 negatively regulates tumor necrosis factor- and interleukin-1-induced nuclear factor-Œ∫B activation by dephosphorylating the protein kinase TAK1
Authors: Xiao He
Jing Zhang
Shu Li
Qi Li
Rui Chen
Yong Ran
Hao Zheng
Hong-Bing Shu
Journal: Journal of Biological Chemistry (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NF-Œ∫B; TAK1; DUSP14; TNF; IL-1
Affiliations: College of Life Sciences, Wuhan University, Wuhan 430072, China.

Abstract:  The transcription factor NF-Œ∫B is critically involved in the inflammatory response triggered by the proinflammatory cytokines TNF and IL-1. Various studies have demonstrated that activation of TAK1 (TGF-Œ≤-activated kinase 1) is an essential step in TNF- and IL-1-induced NF-Œ∫B activation pathways. In this study, we identified a member of the dual-specificity phosphatase family, DUSP14, as a negative regulator of TNF- and IL-1-triggered NF-Œ∫B activation by expression screens. We found that DUSP14 interacted with TAK1 and that this interaction was enhanced by TNF or IL-1 stimulation. Overexpression of DUSP14 dephosphorylated TAK1 at Thr-187, a residue in the activation loop critically involved in TAK1 activation. Knockdown of DUSP14 increased basal as well as TNF- and IL-1-induced TAK1 phosphorylation at Thr-187. Overexpression of DUSP14, but not its phosphatase-deficient mutant, inhibited TNF- and IL-1-induced as well as TAK1-mediated NF-Œ∫B activation, whereas knockdown of DUSP14 had opposite effects. These findings suggest that DUSP14 negatively regulates TNF- or IL-1-induced NF-Œ∫B activation by dephosphorylating TAK1 at Thr-187. Our study reveals a new post-translational regulatory mechanism of NF-Œ∫B activation triggered by the proinflammatory cytokines. 

Retracted: No

PubPeer comments:
 Some WB bands reappeared in Fig.4C.  , 
 #1 I am Hao Zheng, the first author of the paper. The two blots look similar, but different as one can see after enlargement of the photos. Because this paper has been published for 10 years, I have not been able to locate the original data for confirmation. In any cases, the conclusions of the paper are not affected. , 
 #2 In this case, I agree with #1 that these appear unexpectedly similar. ***  , 
 I am Hao Zheng, the first author of the paper. The two blots look similar, but different as one can see after enlargement of the photos. Because this paper has been published for 7 years, I have not been able to locate the original data for confirmation. In any cases, the conclusions of the paper are not affected. , 
 #4 Iu2019m sorry that you are unable to find the original data. My comment was only to confirm that I agree with the original concerns. In my opinion, these bands are probably the same. Unfortunately, without original data, it will be difficult to address reader concerns. I am personally unable to determine whether the possibility that the data does not represent actual experiments is material to the conclusion of your paper. , 
 #4 I agree with #1 and #5. On the basis of the evidence available, in both the published paper and the pre-print version available at JBC , the most likely explanation is that the highlightedregions are identical. That is the safest explanation in the absence of concrete exculpatory evidence. , 
 #1 #4 #5   very interesting! I think it is not exactly same pic. , 
 #7 These minor differences are not meaningful or informative. The published images have obviously undergone compression and or resampling, which degrade the image and can introduce minor apparent differences between what were originally identical images. For an example, see the thread below. In such instances, the relevant question is not whether one can identify some non-identical pixels, but whether the overall patterns make it more likely than not that the two images have a shared origin. https: pubpeer.com publications CB23306078D45C44C2E2F6E556506D#47 ,