Identification of a novel target site for ATP-independent ERK2 inhibitors

AbstractPalmer amaranth (Amaranthus palmeri S. Watson), a dioecious summer annual species, is one of the most troublesome weeds in U.S. cropping systems. The evolution of resistance to protoporphyrinogen oxidase inhibitors in A. palmeri biotypes is a major cause of concern to soybean [Glycine max (L.) Merr.] and cotton (Gossypium hirsutum L.) growers in the midsouthern United States. The objective of this study was to confirm and characterize the non–target site mechanism in a fomesafen-resistant accession from Randolph County, AR (RCA). A dose–response assay was conducted to assess the level of fomesafen resistance, and based on the GR50 values, the RCA accession was 18-fold more resistant to fomesafen than a susceptible (S) biotype. A TaqMan allelic discrimination assay and sequencing of the target-site genes PPX2 and PPX1 revealed no known or novel target-site mutations. An SYBR Green assay indicated no difference in PPX2 gene expression between the RCA and S biotypes. To test whether fomesafen resistance is metabolic in nature, the RCA and the S biotypes were treated with different cytochrome P450 (amitrole, piperonyl butoxide [PBO], malathion) and glutathione S-transferase (GST) (4-chloro-7-nitrobenzofurazan [NBD-Cl]) inhibitors, either alone or in combination with fomesafen. Malathion followed by (fb) fomesafen in RCA showed the greatest reduction in survival (67%) and biomass (86%) compared with fomesafen alone (45% and 66%, respectively) at 2 wk after treatment. Interestingly, NBD-Cl fb fomesafen also resulted in low survival (35%) compared with the fomesafen-only treatment (55%). Applications of malathion or NBD-Cl preceding fomesafen treatment resulted in reversal of fomesafen resistance, indicating the existence of cytochrome P450– and GST-based non–target site mechanisms in the RCA accession. This study confirms the first case of non–target site resistance to fomesafen in A. palmeri.

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Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity

Angewandte Chemie International Edition ◽

10.1002/anie.201506889 ◽

2015 ◽

Vol 54 (44) ◽

pp. 13085-13089 ◽

Cited By ~ 22

Author(s):

Matthew B. Minus ◽

Wei Liu ◽

Farrukh Vohidov ◽

Moses M. Kasembeli ◽

Xin Long ◽

...

Keyword(s):

Target Site ◽

Novel Target

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A Statewide Survey of PPO-Inhibitor Resistance and the Prevalent Target-Site Mechanisms in Palmer amaranth (Amaranthus palmeri) Accessions from Arkansas

Weed Science ◽

10.1017/wsc.2017.68 ◽

2017 ◽

Vol 66 (2) ◽

pp. 149-158 ◽

Cited By ~ 24

Author(s):

Vijay K. Varanasi ◽

Chad Brabham ◽

Jason K. Norsworthy ◽

Haozhen Nie ◽

Bryan G. Young ◽

...

Keyword(s):

Resistance Mechanism ◽

Acetolactate Synthase ◽

Resistance Mechanisms ◽

Palmer Amaranth ◽

Target Site ◽

Evolution Of Resistance ◽

Target Site Resistance ◽

Novel Target ◽

Als Inhibitors ◽

Inhibitor Resistance

Palmer amaranth is one of the most problematic weeds in the midsouthern United States, and the evolution of resistance to protoporphyrinogen oxidase (PPO) inhibitors in biotypes already resistant to glyphosate and acetolactate synthase (ALS) inhibitors is a major cause of concern to soybean and cotton growers in these states. A late-season weed-escape survey was conducted in the major row crop–producing counties (29 counties) to determine the severity of PPO-inhibitor resistance in Arkansas. A total of 227 Palmer amaranth accessions were sprayed with fomesafen at 395 g ha−1to identify putative resistant plants. A TaqMan qPCR assay was used to confirm the presence of the ΔG210 codon deletion or the R128G/M (homologous to R98 mutation in common ragweed) target-site resistance mechanisms in thePPX2gene. Out of the 227 accessions screened, 44 were completely controlled with fomesafen, and 16 had only one or two severely injured plants (≥98% mortality) when compared with the 1986 susceptible check (100% mortality). The remaining 167 accessions were genotypically screened, and 82 (49%) accessions were found to harbor the ΔG210 deletion in thePPX2gene. The R128G was observed in 47 (28%) out of the 167 accessions screened. The mutation R128M, on the other hand was rare, found in only three accessions. About 13% of the accessions were segregating for both the ΔG210 and R128G mutations. Sixteen percent of the tested accessions had mortality ratings <90% and did not test positive for the ΔG210 or the R128G/M resistance mechanisms, indicating that a novel target or non–target site resistance mechanism is likely. Overall, PPO inhibitor–resistant Palmer amaranth is widespread in Arkansas, and the ΔG210 resistance mechanism is especially dominant in the northeast corridor, while the R128G mutation is more prevalent in counties near Memphis, TN.

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