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Nature Chemical Biology Contents: May 2016, Volume 12 No 5 pp 305 - 379

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TABLE OF CONTENTS

May 2016 Volume 12, Issue 5

Research Highlights
News and Views
Articles

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Research Highlights

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Kinase regulation: Shortening the loop | Protein synthesis: Taming transmembrane proteins | RNA trafficking: RCas9 lights the way | Inflammation: Dietary stress relief


News and Views

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Optoepigenetics: An acetylation photoswitch   pp306 - 307
Andreas S Madsen and Christian A Olsen
doi:10.1038/nchembio.2049
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.

See also: Article by Reis et al.

Oxidative stress: Bioplastic hydroxyl radical trapping   pp307 - 308
Joris Messens
doi:10.1038/nchembio.2058
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.

See also: Article by Koskimaki et al.

Immunology: JAK3 inhibition—is it sufficient?   pp308 - 310
Warren J Leonard, Suman Mitra and Jian-Xin Lin
doi:10.1038/nchembio.2066
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.

See also: Article by Smith et al.

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Articles

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Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome   pp311 - 316
Xiaoyu Li, Xushen Xiong, Kun Wang, Lixia Wang, Xiaoting Shu et al.
doi:10.1038/nchembio.2040



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[prime] UTRs of human genes.

Light-controlled modulation of gene expression by chemical optoepigenetic probes   pp317 - 323
Surya A Reis, Balaram Ghosh, J Adam Hendricks, D Miklos Szantai-Kis, Lisa Tork et al.
doi:10.1038/nchembio.2042



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.
Chemical compounds
See also: News and Views by Madsen & Olsen

Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation   pp324 - 331
Kuan-Chuan Pao, Mathew Stanley, Cong Han, Yu-Chiang Lai, Paul Murphy et al.
doi:10.1038/nchembio.2045



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.
Chemical compounds

Methyl-esterified 3-hydroxybutyrate oligomers protect bacteria from hydroxyl radicals   pp332 - 338
Janne J Koskimaki, Marena Kajula, Juho Hokkanen, Emmi-Leena Ihantola, Jong H Kim et al.
doi:10.1038/nchembio.2043



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.

See also: News and Views by Messens

Exploiting nongenetic cell-to-cell variation for enhanced biosynthesis   pp339 - 344
Yi Xiao, Christopher H Bowen, Di Liu and Fuzhong Zhang
doi:10.1038/nchembio.2046



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.

Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage   pp345 - 352
Ling Liu, Supriya Shah, Jing Fan, Junyoung O Park, Kathryn E Wellen et al.
doi:10.1038/nchembio.2047



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.

Steric trapping reveals a cooperativity network in the intramembrane protease GlpG   pp353 - 360
Ruiqiong Guo, Kristen Gaffney, Zhongyu Yang, Miyeon Kim, Suttipun Sungsuwan et al.
doi:10.1038/nchembio.2048



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.
Chemical compounds

Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification   pp361 - 366
Richard M Deans, David W Morgens, Ayse Okesli, Sirika Pillay, Max A Horlbeck et al.
doi:10.1038/nchembio.2050



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.
Chemical compounds

AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs   pp367 - 372
William H Parsons, Matthew J Kolar, Siddhesh S Kamat, Armand B Cognetta III, Jonathan J Hulce et al.
doi:10.1038/nchembio.2051



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.
Chemical compounds

Essential biphasic role for JAK3 catalytic activity in IL-2 receptor signaling   pp373 - 379
Geoffrey A Smith, Kenji Uchida, Arthur Weiss and Jack Taunton
doi:10.1038/nchembio.2056



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.
Chemical compounds
See also: News and Views by Leonard et al.

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