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Casein kinase 1 alpha (CK1α) is a serine/threonine kinase with numerous functions, including regulating the Wnt/β‐catenin and p53 pathways. CK1α has a well‐established role in inhibiting the p53 tumor suppressor by binding to MDMX and stimulating MDMX‐p53 interaction. MDMX purified from cells contains near‐stoichiometric amounts of CK1α, suggesting that MDMX may in turn regulate CK1α function. We present evidence that MDMX is a potent competitive inhibitor of CK1α kinase activity (Ki = 8 nM). Depletion of MDMX increases CK1α activity and β‐catenin S45 phosphorylation, whereas ectopic MDMX expression inhibits CK1α activity and β‐catenin phosphorylation. The MDMX acidic domain and zinc finger are necessary and sufficient for binding and inhibition of CK1α. P53 binding to MDMX disrupts an intramolecular auto‐regulatory interaction and enhances its ability to inhibit CK1α. P53‐null mice expressing the MDMXW200S/W201G mutant, defective in CK1α binding, exhibit reduced Wnt/β‐catenin target gene expression and delayed tumor development. Therefore, MDMX is a physiological inhibitor of CK1α and has a role in modulating cellular response to Wnt signaling. The MDMX‐CK1α interaction may account for certain p53‐independent functions of MDMX. Synopsis: MDMX cooperates with casein kinase 1α to bind and inhibit the tumor suppressor p53. Here, the MDMX‐CK1α interaction is found to also block the ability of CK1α to phosphorylate β‐catenin and to suppress canonical Wnt signaling. MDMX is a potent competitive inhibitor of CK1α kinase activity, with a Ki of 8 nM.MDMX knockdown increases CK1α activity and β‐catenin Ser45 phosphorylation.MDMX mutation in p53‐null mice reduces Wnt signaling and delays tumor development.MDMX‐CK1α interaction is a growth‐promoting mechanism independent of p53. [ABSTRACT FROM AUTHOR]

Glyphosate ( N-phosphonomethyl-glycine) is the most widely used herbicide in the world: glyphosate-based formulations exhibit broad-spectrum herbicidal activity with minimal human and environmental toxicity. The extraordinary success of this simple, small molecule is mainly attributable to the high specificity of glyphosate for the plant enzyme enolpyruvyl shikimate-3-phosphate synthase in the shikimate pathway, leading to the biosynthesis of aromatic amino acids. Starting in 1996, transgenic glyphosate-resistant plants were introduced, thus allowing application of the herbicide to the crop (post-emergence) to remove emerged weeds without crop damage. This review focuses on mechanisms of resistance to glyphosate as obtained through natural diversity, the gene-shuffling approach to molecular evolution, and a rational, structure-based approach to protein engineering. In addition, we offer a rationale for the means by which the modifications made have had their intended effect. [ABSTRACT FROM AUTHOR]