SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate

September 6th, 2018 by Mary E. Matyskiela

SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate

SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate, Published online: 06 September 2018; doi:10.1038/s41589-018-0129-x

Thalidomide-induced degradation of the transcription factor SALL4 in a cereblon-dependent manner provides an explanation for the teratogenic effects.
  • Posted in Nat Chem Biol, Publications
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[ASAP] Targeting Fluorescent Sensors to Endoplasmic Reticulum Membranes Enables Detection of Peroxynitrite During Cellular Phagocytosis

September 4th, 2018 by Kelsey E. Knewtson, Digamber Rane, Blake R. Peterson

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ACS Chemical Biology
DOI: 10.1021/acschembio.8b00535
  • Posted in ACS Chemical Biology, Publications
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[ASAP] Tamoxifen- and Mifepristone-Inducible Versions of CRISPR Effectors, Cas9 and Cpf1

September 3rd, 2018 by Alazne Dominguez-Monedero, Jamie A. Davies

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.8b00145

[ASAP] Optimization of Artificial Curcumin Biosynthesis in <italic toggle=”yes”>E. coli</italic> by Randomized 5′-UTR Sequences To Control the Multienzyme Pathway

September 3rd, 2018 by Sun-Young Kang, Kyung Taek Heo, Young-Soo Hong

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.8b00198
  • Posted in ACS Synthetic Biology, Publications
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Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

September 3rd, 2018 by Salma Akter

Chemical proteomics reveals new targets of cysteine sulfinic acid reductase

Chemical proteomics reveals new targets of cysteine sulfinic acid reductase, Published online: 03 September 2018; doi:10.1038/s41589-018-0116-2

An electrophilic diazene probe (DiaAlk) enables capture and proteomic analysis of cysteine S-sulfinylation modifications, thus illuminating dynamic responses to oxidative stress and enabling the identification of new substrates of sulfiredoxin.
  • Posted in Nat Chem Biol, Publications
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Substrate-assisted enzymatic formation of lysinoalanine in duramycin

September 3rd, 2018 by Linna An

Substrate-assisted enzymatic formation of lysinoalanine in duramycin

Substrate-assisted enzymatic formation of lysinoalanine in duramycin, Published online: 03 September 2018; doi:10.1038/s41589-018-0122-4

During the biosynthesis of the lanthipeptide duramycin, DurN catalyzes stereospecific lysinoalanine formation by preorganizing the reactive conformation of the substrate, such that one of the substrate’s own residues serves as the catalytic base.

Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit

September 3rd, 2018 by Ravikrishna Ramanujam

Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit

Establishment of the PAR-1 cortical gradient by the aPKC-PRBH circuit, Published online: 03 September 2018; doi:10.1038/s41589-018-0117-1

The asymmetric cortical gradient of PAR-1 is patterned via an integration of its cortical exclusion and stabilization by a circuit consisting of aPKC and the PRBH protein PAR-2.
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RNF144A Sustains EGFR Signaling to Promote EGF-Dependent Cell Proliferation [Protein Synthesis and Degradation]

August 31st, 2018 by Shiuh-Rong Ho, Weei-Chin Lin

RNF144A is a single-pass transmembrane RBR E3 ligase that interacts with and degrades cytoplasmic DNA-PKcs, which is an EGFR-interacting partner. Interestingly, RNF144A expression is positively correlated with EGFR mRNA and protein levels in several types of cancer. However, the relationship between RNF144A and EGFR is poorly understood. This study reports an unexpected role for RNF144A in the regulation of EGF/EGFR signaling and EGF-dependent cell proliferation. EGFR ligands, but not DNA-damaging agents, induce a DNA-PKcs-independent interaction between RNF144A and EGFR. RNF144A promotes EGFR ubiquitination, maintains EGFR protein and prolongs EGF/EGFR signaling during EGF stimulation. Moreover, depletion of RNF144A by multiple independent approaches results in a decrease in EGFR expression and EGF/EGFR signaling. RNF144A knockout cells also fail to mount an immediate response to EGF for activation of G1/S progression genes. Consequently, depletion of RNF144A reduces EGF-dependent cell proliferation. These defects may be at least in part due to a role for RNF144A in regulating EGFR transport in the intracellular vesicles during EGF treatment.

Identification of a Kdn biosynthesis pathway in the haptophyte Prymnesium parvum suggests widespread sialic acid biosynthesis among microalgae [Enzymology]

August 31st, 2018 by Ben A Wagstaff, Martin Rejzek, Robert A. Field

Sialic acids are a family of more than 50 structurally distinct acidic sugars on the surface of all vertebrate cells where they terminate glycan chains and are exposed to many interactions with the surrounding environment. In particular, sialic acids play important roles in cell-cell and host-pathogen interactions. The sialic acids or related nonulosonic acids have been observed in Deuterostome lineages, Eubacteria, and Archaea, but are notably absent from plants. However, the structurally related C8 acidic sugar, 3-deoxy-D-manno-2-octulosonic acid (Kdo), is present in Gram-negative bacteria and plants as a component of bacterial lipopolysaccharide and pectic rhamnogalacturonan-II in the plant cell wall. Until recently, sialic acids were not thought to occur in algae, but as in plants, Kdo has been observed in algae. Here, we report the de novo biosynthesis of the deaminated sialic acid, 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (Kdn), in the toxin-producing microalga Prymnesium parvum. Using biochemical methods, we show that this alga contains CMP–Kdn and identified and recombinantly expressed the P. parvum genes encoding Kdn-9-P synthetase and CMP-Kdn synthetase enzymes that convert mannose-6-P to CMP–Kdn. Bioinformatics analysis revealed sequences related to those of the two P. parvum enzymes, suggesting that sialic acid biosynthesis is likely more widespread among microalgae than previously thought and that this acidic sugar may play a role in host-pathogen interactions involving microalgae. Our findings provide evidence that P. parvum has the biosynthetic machinery for de novo production of the deaminated sialic acid Kdn and that sialic acid biosynthesis may be common among microalgae.
  • Posted in Journal of Biological Chemistry, Publications
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Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis

August 27th, 2018 by Takaaki Taniguchi

Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis

Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis, Published online: 27 August 2018; doi:10.1038/s41589-018-0119-z

A comparative genomic approach identified a novel acetate-dependent tRNA-modifying enzyme that catalyzes RNA acetylation with a mechanism similar to tRNA aminoacylation. This modification maintains decoding fidelity in protein synthesis.
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