NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint
Authors: Kristian Helin
Claus Storgaard Sørensen
Marina Melixetian
Ditte Kjaersgaard Klein
Journal: Nature Cell Biology (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DNA damage; cell-cycle checkpoints; CDC25A; NEK11; G2/M checkpoint
Affiliations: Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20135, Milan, Italy.

Abstract:  DNA damage-induced cell-cycle checkpoints have a critical role in maintaining genomic stability. A key target of the checkpoints is the CDC25A (cell division cycle 25 homologue A) phosphatase, which is essential for the activation of cyclin-dependent kinases and cell-cycle progression. To identify new genes involved in the G2/M checkpoint we performed a large-scale short hairpin RNA (shRNA) library screen. We show that NIMA (never in mitosis gene A)-related kinase 11 (NEK11) is required for DNA damage-induced G2/M arrest. Depletion of NEK11 prevents proteasome-dependent degradation of CDC25A, both in unperturbed and DNA-damaged cells. We show that NEK11 directly phosphorylates CDC25A on residues whose phosphorylation is required for beta-TrCP (beta-transducin repeat-containing protein)-mediated polyubiquitylation and degradation of CDC25A. Furthermore, we demonstrate that CHK1 (checkpoint kinase 1) directly activates NEK11 by phosphorylating it on Ser 273, indicating that CHK1 and NEK11 operate in a single pathway that controls proteolysis of CDC25A. Taken together, these results demonstrate that NEK11 is an important component of the pathway enforcing the G2/M checkpoint, suggesting that genetic mutations in NEK11 may contribute to the development of human cancer. 

Retracted: No

PubPeer comments:
 Image concerns in this paper were found during a systematic search of papers in Spandidos journals for possible duplicated images. Figure 2B. Pink boxes: The top left part of this panel appears to show the same group of cells two times. ![file] , 
 Figure 3. The top left corner of panels A, C, and D, and possibly that of panel C appear to show repetitive features. Boxes of the same color highlight areas that look similar to each other. ![file] , 
 Figure 4, in what appears to be a homage to Monet s Nymphu00e9as series of paintings, appears to contain several repetitive waterlilies, both between and within panels. Boxes of the same color highlight areas that look similar to each other. ![file] , 
 #2 Fig 3 again: ![] Compare with Figure 8 from [Chen et al (2019)] .  Inhibition of cell invasion in A375 human malignant melanoma cells. The cells were treated with 0 (A), 50 (B), 150 (C) and 300 (D) u00b5M doses of methylwogonin for 48 h . ![] , 
 #1 *[left]* Fig 2 again. *[right]* Figure 5 from [Xu et al (2019)] .  Totarol led to inhibition of migration in SGC-7901 human gastric cancer cells. Cells were treated with 0 (B), 40 (C), 100 (D) and 400 (E) u00b5M dose of totarol. A shows a simulated wound prepared by scratching with a micropipette tip. ![file] The glitched areas at the upper left corner of each panel (presumably from filing off the original ID) are different in the two versions. It may be that they are both copied from an unknown original. , 
 Retracted [12 April 2021] .  Following the publication of the above paper, a concerned reader drew to the Editor s attention that several figures (specifically, Figs. 2, 3 and 4) contained apparent anomalies, including repeated patternings of data within the same figure panels.  After having conducted an independent investigation in the Editorial Office, the Editor of Oncology Letters has determined that this paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. ,