Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol

December 26th, 2016 by Shu-Lin Liu

Nature Chemical Biology 13, 268 (2017). doi:10.1038/nchembio.2268

Authors: Shu-Lin Liu, Ren Sheng, Jae Hun Jung, Li Wang, Ewa Stec, Matthew J O'Connor, Seohyoen Song, Rama Kamesh Bikkavilli, Robert A Winn, Daesung Lee, Kwanghee Baek, Kazumitsu Ueda, Irena Levitan, Kwang-Pyo Kim & Wonhwa Cho

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol

RIT1 GTPase Regulates Sox2 Transcriptional Activity and Hippocampal Neurogenesis [Signal Transduction]

December 22nd, 2016 by Sajad Mir, Weikang Cai, Douglas A. Andres

Adult neurogenesis, the process of generating mature neurons from neuronal progenitor cells, makes critical contributions to neural circuitry and brain function under both healthy and disease states. Neurogenesis is a highly regulated process, in which diverse environmental and physiological stimuli are relayed to resident neural stem cell populations to control the transcription of genes involved in their self-renewal and differentiation. Understanding the molecular mechanisms governing neurogenesis is necessary for the development of translational strategies to harness this process for neuronal repair. Here we report that the Ras-related GTPase, RIT1, serves to control the sequential proliferation and differentiation of adult hippocampal neural/stem progenitor cells (NPCs), with in vivo expression of active RIT1 driving robust adult neurogenesis. Gene expression profiling analysis demonstrates increased expression of a specific set of transcription factors known to govern adult neurogenesis in response to active RIT1 expression in the hippocampus, including sex-determining region Y-related HMG box 2 (Sox2), a well-established regulator of stem cell self-renewal and neurogenesis. In adult hippocampal neuronal precursor cells (HNPCs), RIT1 controls an Akt-dependent signaling cascade, resulting in the stabilization and transcriptional activation of phosphorylated Sox2. Together, these studies support a role for RIT1 in relaying niche-derived signals to NPCs to control transcription of genes involved in self-renewal and differentiation.

Can Reduction of NO to N2O in Cytochrome c Dependent Nitric Oxide Reductase Proceed through a Trans-Mechanism?

December 21st, 2016 by Margareta R. A. Blomberg

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.6b00788

Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase

December 19th, 2016 by Ridao Chen

Nature Chemical Biology 13, 226 (2017). doi:10.1038/nchembio.2263

Authors: Ridao Chen, Bingquan Gao, Xiao Liu, Feiying Ruan, Yong Zhang, Jizhong Lou, Keping Feng, Carsten Wunsch, Shu-Ming Li, Jungui Dai & Fei Sun

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase

Orphan receptor ligand discovery by pickpocketing pharmacological neighbors

December 19th, 2016 by Tony Ngo

Nature Chemical Biology 13, 235 (2017). doi:10.1038/nchembio.2266

Authors: Tony Ngo, Andrey V Ilatovskiy, Alastair G Stewart, James L J Coleman, Fiona M McRobb, R Peter Riek, Robert M Graham, Ruben Abagyan, Irina Kufareva & Nicola J Smith

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Orphan receptor ligand discovery by pickpocketing pharmacological neighbors

Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence

December 19th, 2016 by Huiqing Zheng

Nature Chemical Biology 13, 218 (2017). doi:10.1038/nchembio.2259

Authors: Huiqing Zheng, Christopher J Colvin, Benjamin K Johnson, Paul D Kirchhoff, Michael Wilson, Katriana Jorgensen-Muga, Scott D Larsen & Robert B Abramovitch

  • Posted in Nat Chem Biol, Publications
  • Comments Off on Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence

A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling

December 19th, 2016 by Rahul S Kathayat

Nature Chemical Biology 13, 150 (2017). doi:10.1038/nchembio.2262

Authors: Rahul S Kathayat, Pablo D Elvira & Bryan C Dickinson

Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoylation, acylprotein thioesterases (APTs). Live-cell analysis with DPPs reveals rapid growth-factor-mediated inhibition of the depalmitoylation activity of APTs, exposing a novel regulatory mechanism of dynamic lipid signaling.

  • Posted in Nat Chem Biol, Publications
  • Comments Off on A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling

RAS signaling: Divide and conquer

December 16th, 2016 by Matthew Holderfield

Nature Chemical Biology 13, 7 (2017). doi:10.1038/nchembio.2264

Authors: Matthew Holderfield & Deborah K Morrison

The role of RAS dimerization in tumor biology is an emerging area of preclinical cancer research. Characterization of a RAS monobody indicates that dimer formation is required for RAS signaling, revealing the dimer interface as a potential drug target.

Natural products: Mapping an amazing thicket

December 16th, 2016 by Mark E Horsman

Nature Chemical Biology 13, 6 (2017). doi:10.1038/nchembio.2265

Authors: Mark E Horsman & Christopher N Boddy

The Global Natural Products Social Molecular Networking (GNPS) resource and the DEREPLICATOR algorithm provide new tools for analyzing mass spectral data and enabling natural products discovery.

RNA structure: Widening the probe

December 16th, 2016 by Grant Miura

Nature Chemical Biology 13, 1 (2017). doi:10.1038/nchembio.2274

Author: Grant Miura