Loss of protein association causes cardiolipin degradation in Barth syndrome

June 27th, 2016 by Yang Xu

Nature Chemical Biology 12, 641 (2016). doi:10.1038/nchembio.2113

Authors: Yang Xu, Colin K L Phoon, Bob Berno, Kenneth D'Souza, Esthelle Hoedt, Guoan Zhang, Thomas A Neubert, Richard M Epand, Mindong Ren & Michael Schlame

  • Posted in Nat Chem Biol, Publications
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Preincubation of t-SNAREs with Complexin I Increases Content-Mixing Efficiency

June 24th, 2016 by Jaewook Kim, Yicheng Zhu and Yeon-Kyun Shin

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Biochemistry
DOI: 10.1021/acs.biochem.6b00114

NEDD4L Catalyzes Ubiquitination of PIK3CA and Regulates PI3K-AKT Signaling [Signal Transduction]

June 23rd, 2016 by Wang, Z., Dang, T., Liu, T., Chen, S., Li, L., Huang, S., Fang, M.

Oncogenic PIK3CA (p110α), the catalytic subunit of class IA PI3K, plays a major role in PI3K related cancer progression. The mechanisms underlying the dynamic regulation of PIK3CA protein levels remain unknown. Here we demonstrated that PIK3CA is regulated by polyubiquitination. We identified NEDD4L as the E3 ligase that catalyzes PIK3CA polyubiquitination, leading to its proteasome-dependent degradation. NEDD4L ubiquitinates both the free and regulatory subunit-bound PIK3CA, but does not ubiquitinate the regulatory subunit of PI3K. Overexpression of NEDD4L accelerates the turnover rate of PIK3CA whereas suppression of NEDD4L results in not only the accumulation of PIK3CA but also a paradoxical decrease of AKT activation. Thus, we propose that NEDD4L negatively regulates PIK3CA protein levels via ubiquitination and is required for the maintenance of PI3K-AKT signaling pathway.

Identifying the functional contribution of the defatty-acylase activity of SIRT6

June 20th, 2016 by Xiaoyu Zhang

Nature Chemical Biology 12, 614 (2016). doi:10.1038/nchembio.2106

Authors: Xiaoyu Zhang, Saba Khan, Hong Jiang, Marc A Antonyak, Xiao Chen, Nicole A Spiegelman, Jonathan H Shrimp, Richard A Cerione & Hening Lin

  • Posted in Nat Chem Biol, Publications
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A family of metal-dependent phosphatases implicated in metabolite damage-control

June 20th, 2016 by Lili Huang

Nature Chemical Biology 12, 621 (2016). doi:10.1038/nchembio.2108

Authors: Lili Huang, Anna Khusnutdinova, Boguslaw Nocek, Greg Brown, Xiaohui Xu, Hong Cui, Pierre Petit, Robert Flick, Rémi Zallot, Kelly Balmant, Michael J Ziemak, John Shanklin, Valérie de Crécy-Lagard, Oliver Fiehn, Jesse F Gregory, Andrzej Joachimiak, Alexei Savchenko, Alexander F Yakunin & Andrew D Hanson

  • Posted in Nat Chem Biol, Publications
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Cooperation of local motions in the Hsp90 molecular chaperone ATPase mechanism

June 20th, 2016 by Andrea Schulze

Nature Chemical Biology 12, 628 (2016). doi:10.1038/nchembio.2111

Authors: Andrea Schulze, Gerti Beliu, Dominic A Helmerich, Jonathan Schubert, Laurence H Pearl, Chrisostomos Prodromou & Hannes Neuweiler

  • Posted in Nat Chem Biol, Publications
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Sialylation of GPI Anchors of Mammalian Prions is Regulated in a Host-, Tissue- and Cell-Specific Manner [Glycobiology and Extracellular Matrices]

June 17th, 2016 by Katorcha, E., Srivastava, S., Klimova, N., Baskakov, I. V.

Prions or PrPSc are proteinaceous infectious agents that consist of misfolded, self-replicating states of the prion protein or PrPC. PrPC is posttranslationally modified with N-linked glycans and a sialylated glycosylinositol phospholipid anchor (GPI). Conformational conversion of PrPC give rise to glycosylated and GPI-anchored PrPSc. The question of the sialylation status of GPIs within PrPSc has been controversial. Previous studies that examined scrapie brains reported that both sialo- and asialo-GPIs were present in PrPSc with the majority being asialo-GPIs. In contrast, recent work that employed cultured cells claimed that only PrPC with sialylo-GPIs could be recruited into PrPSc, whereas PrPC with asialo-GPIs inhibited conversion. To resolve this controversy, we analyzed sialylation status of GPIs within PrPSc generated in brain, spleen, or cultured N2a or C2C12 myotube cells. We found that recruiting PrPC with both sialo- and asialo-GPIs is a common feature of PrPSc. The mixtures of sialo- and asialo-GPIs were observed in PrPSc universally regardless of prion strain, as well as host, tissue or type of cells that produced PrPSc. Remarkably, the proportion of sialo- versus asialo-GPIs was found to be controlled by host, tissue and cell type, but not prion strain. In summary, the current study found no strain-specific preferences for selecting PrPC with sialo- versus asialo-GPIs. Instead, this work suggests that the sialylation status of GPIs within PrPSc is regulated in a cell-, tissue- or host-specific manner, and is likely to be determined by the specifics of GPI biosynthesis.
  • Posted in Journal of Biological Chemistry, Publications
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Effects of Macromolecular Crowding on Alcohol Dehydrogenase Activity Are Substrate-Dependent

June 17th, 2016 by A. E. Wilcox, Micaela A. LoConte and Kristin M. Slade

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Biochemistry
DOI: 10.1021/acs.biochem.6b00257

Ion channels: Calcium channels work together

June 17th, 2016 by Mirella Bucci

Nature Chemical Biology 12, 467 (2016). doi:10.1038/nchembio.2123

Author: Mirella Bucci

Chemical genetics: Unraveling cell death mysteries

June 17th, 2016 by Xiomaris M Cotto-Rios

Nature Chemical Biology 12, 470 (2016). doi:10.1038/nchembio.2110

Authors: Xiomaris M Cotto-Rios & Evripidis Gavathiotis

Non-apoptotic regulated cell death is not fully characterized, particularly for ferroptosis, the iron- and ROS-dependent form of regulated cell death. A systematic approach using modulatory profiling and cell line sensitivity analysis has unraveled the association of lipid metabolism with ferroptosis and enabled the discovery of a novel specific ferroptosis inducer.