Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ.

Pseudokinases are considered to be the inactive counterparts of conventional protein kinases and comprise approximately 10% of the human and mouse kinomes. Here, we report the crystal structure of the effector protein, SidJ, in complex with the eukaryotic Ca-binding regulator, calmodulin (CaM). The structure reveals that SidJ contains a protein kinase-like fold domain, which retains a majority of the characteristic kinase catalytic motifs.

Hypoxia drives transient site-specific copy gain and drug-resistant gene expression.

Copy number heterogeneity is a prominent feature within tumors. The molecular basis for this heterogeneity remains poorly characterized. Here, we demonstrate that hypoxia induces transient site-specific copy gains (TSSGs) in primary, nontransformed, and transformed human cells.

A coding single-nucleotide polymorphism in lysine demethylase KDM4A associates with increased sensitivity to mTOR inhibitors.

Unlabelled: SNPs occur within chromatin-modulating factors; however, little is known about how these variants within the coding sequence affect cancer progression or treatment. Therefore, there is a need to establish their biochemical and/or molecular contribution, their use in subclassifying patients, and their impact on therapeutic response. In this report, we demonstrate that coding SNP-A482 within the lysine tridemethylase gene KDM4A/JMJD2A has different allelic frequencies across ethnic populations, associates with differential outcome in patients with non-small cell lung cancer (NSCLC), and promotes KDM4A protein turnover.