Volume 12 Issue 5, May 2016

Histone 3 lysine 9 acetylation (H3K9ac) levels were modulated by photoresponsive histone deacetylase (HDAC) inhibitors to perturb the transcription of genes involved in cell cycle regulation and mitochondrial function.

The hydroxyl radical is the reactive oxygen species most cytotoxic to cells. A bioplastic-based hydroxyl radical scavenger that is more efficient than glutathione and vitamin C has been found to be produced by bacteria, adding an interesting twist to the story of oxidative stress defense by intracellular pathogens.

A highly selective JAK3 inhibitor with subnanomolar potency has been used to identify two waves of STAT5 phosphorylation in response to IL-2. This reveals a biphasic role for JAK3 catalytic activity in IL-2-mediated signaling that has therapeutic implications.

A method called m¹A-ID-seq, which involves antibody enrichment and reverse transcriptase–based sequencing of N¹-methyladenosine (m¹A) RNA modifications, reveals that m¹A is a reversible mRNA modification that is abundant in the 5′ UTRs of human genes.

An approach called chemo-optical modulation of epigenetically regulated transcription (COMET) combines azobenzene-based photochromic HDAC inhibitors with microprocessor-controlled LED plates to regulate gene expression profiles in a light-dependent manner.

Probes of E3 ligase transthiolation activity reveal the hierarchy of phosphorylation events leading to cellular parkin activation and show that disease-linked parkin mutants have impaired transthiolation activity.

Methylobacterium extorquens living in shoots and roots of Pinus sylvestris expresses poly-3-hydroxybutyrate (PHB) synthase and PHB depolymerase to generate methyl-esterified dimers and trimers of 3-hydroxybutyrate that greatly increase bacterial tolerance to host-induced oxidative stress.

An approach termed in vivo population quality control, which is coordinated by a metabolite biosensor-survival gene circuit, takes advantage of cell-to-cell variation to optimize production of selected metabolites in isogenic Escherichia coli cultures.

The development of metabolic tracers reveals that malic enzyme is the main contributor of NADPH production in differentiating adipocytes. During hypoxic conditions, the source of NADPH shifts to the oxidative pentose phosphate pathway.

A steric trapping method for monitoring membrane protein folding under native conditions shows an expanded unfolded state of the GlpG intramembrane protease and identifies a network of cooperative interactions at side chain resolution for maintaining its stability.

A combination of shRNA- and CRISPR-Cas9-based gene editing screens, corroborated by a metabolite suppression experiment identifies the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) as the target of the broad-spectrum antiviral compound GSK983.

Activity-based protein profiling identifies AIG1 and ADTRPP as transmembrane threonine hydrolases with substrates that include several fatty acid esters of hydroxyl fatty acids (FAHFAs). New inhibitors of these enzymes inhibit FAHFA hydrolysis.

The use of a selective JAK3 covalent inhibitor reveals two distinct temporal waves of STAT5 phosphorylation. The inhibitor more potently targets the second wave, which is required for cell cycle progression and T cell proliferation.