The oncogene KRAS not only promotes the tumorigenesis of pancreatic cancers but also is required for the malignant progression and metastasis of these cancers. Many methods have been explored to influence the malignant biological behavior of these cancers by targeting mutant KRAS. The ornithine decarboxylase/antizyme (ODC/AZ) system is another protein degradation pathway that exists in nature. The formation of an ODC and protein substrate complex through direct combination can promote its degradation by the 26S proteasome without ubiquitination, and this process can be catalyzed by AZ. In this study, we designed and reconstructed a chimeric fusion protein (named RC‐ODC). The engineered fusion protein RC‐ODC was confirmed to interact with the mutant KRAS oncoprotein in a co‐immunoprecipitation assay, and the introduction of both RC‐ODC and AZ resulted in degradation of the exogenous and endogenous mutant KRAS oncoprotein at the post‐translational level independent of ubiquitination in vitro. Along with a decreased KRAS level, suppression of PANC‐1 cell proliferation was detected in vitro and in vivo, and meanwhile downregulation of phosphorylated extracellular signal‐regulated kinase 1/2 (ERK1/2) was also observed. Targeted degradation of the KRAS oncoprotein through the ODC/AZ pathway at the post‐translational level may reflect a more effective future therapeutic strategy for pancreatic cancer patients. © 2018 The Authors. IUBMB Life published by Wiley Periodicals,Inc. on behalf of International Union of Biochemistry and Molecular Biology, 1‐9, 2018

Sugar beet cytoplasmic male sterility (CMS) underpins hybrid seed production, yet the contribution of protein phosphorylation remains unexplored. Using 4D label-free phosphoproteomics on anthers of the Owen-type CMS line MS327 and its maintainer OT328 at the 2–3 mm bud stage, we identified 1241 phosphoproteins, 1975 phosphopeptides and 3357 phosphosites, of which 469 proteins and 848 sites were quantifiable. Twenty-one phosphopeptides exhibited significant differential abundance (fold change > 2.0, p < 0.05; 3 up, 18 down), while 69 and 141 peptides were detected exclusively in the maintainer and the sterile line, respectively. Pathway enrichment implicated the spliceosome and fatty acid elongation pathways in male sterility. Integrating KEGG, GO and predicted protein–protein interaction networks analyses, we identified nuclear cap-binding protein subunit 2 (NCBP2), the RRM-containing splicing factor SR45a and 3-ketoacyl-CoA synthase as candidate phosphoproteins associated with male sterility. All six core proteins were deeply conserved across the examined species. Although transcript levels of the six corresponding genes did not differ significantly between the two lines in either leaf or anthers, anther phosphorylation levels did, pointing to post-translational rather than transcriptional control. This first phosphoproteomic survey of sugar beet CMS provides a valuable readout of post-translational reprogramming and offers promising candidate targets for future functional validation.