Dataset Information

Effect of Sec61 inhibitor mycolactone on the proteome of the MED17.11 neuronal cell line

ABSTRACT: Mycolactone is a mycobacteria-derived macrolide that blocks the biogenesis of a large array of secreted and transmembrane proteins through potent inhibition of the Sec61 translocon. Here, we used quantitative proteomics to delineate the direct and indirect effects of mycolactone-mediated Sec61 blockade on mouse on MED17.11 cells, as a model of dorsal root ganglia (DRG) sensory neurons, in resting and LPS-stimulated conditions. This analysis completes two previously reported ones, which investigated the effects of mycolactone on the proteome of the mouse MutuDC dendritic cells (Project PXD006103) and human Jurkat T cells (Project PXD002971).

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Permanent Cell Line Cell, Cell Culture, Sensory Neuron Of Dorsal Root Ganglion

SUBMITTER: Jean-David Morel

LAB HEAD: Caroline Demangel

PROVIDER: PXD007770 | Pride | 2018-06-26

REPOSITORIES: Pride

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Publications

Proteomics Reveals Scope of Mycolactone-mediated Sec61 Blockade and Distinctive Stress Signature.

Morel Jean-David JD Paatero Anja O AO Wei Jiajie J Yewdell Jonathan W JW Guenin-Macé Laure L Van Haver Delphi D Impens Francis F Pietrosemoli Natalia N Paavilainen Ville O VO Demangel Caroline C

Molecular & cellular proteomics : MCP 20180618 9

Mycolactone is a bacteria-derived macrolide that blocks the biogenesis of a large array of secretory and integral transmembrane proteins (TMP) through potent inhibition of the Sec61 translocon. Here, we used quantitative proteomics to delineate the direct and indirect effects of mycolactone-mediated Sec61 blockade in living cells. In T lymphocytes, dendritic cells and sensory neurons, Sec61 substrates downregulated by mycolactone were in order of incidence: secretory proteins (with a signal pept ...[more]

PMID: 29915147

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Project description:Glioblastoma multiforme (GBM) is the most prevalent type of adult brain tumor, and one of the deadliest tumors known to mankind. The genetic understanding of GBM is, however, limited, and the molecular mechanisms which facilitate GBM cell survival and growth within the tumor microenvironment are largely unknown. We applied digital karyotyping and single nucleotide polymorphism (SNP) arrays to screen for copy number changes in GBM samples and found that the most frequently amplified region is at chromosome 7p11.2. The high resolution of digital karyotyping and SNP arrays permits the precise delineation of amplicon boundaries and has enabled identification of the minimal region of amplification at 7p11.2, which contains two genes, EGFR and SEC61?. SEC61? encodes a subunit of a heterotrimeric protein channel located in the endoplasmic reticulum (ER). In addition to its high frequency of gene amplification in GBMs, SEC61? is also remarkably overexpressed in 77% of GBMs, but not in lower-grade gliomas. The siRNA-mediated knockdown of SEC61? expression in tumor cells led to growth suppression and apoptosis. Furthermore, we showed that pharmacological ER stress agents induce SEC61? expression in GBM cells. Together, these results indicate that aberrant expression of SEC61? serves significant roles in GBM cell survival, likely via a mechanism that is involved in the cytoprotective ER stress-adaptive response to the tumor microenvironment. hSETD1A was silenced in HCT116 cells using retrovirus harboring shRNA specifically against the hSETD1A gene. 10?g RNA was reverse transcribed to cDNA using the Applied Biosystems High Capacity cDNA Reverse Transcription kit according to the manufacturer’s instructions (Applied Biosystems). cDNA products were treated with 100ng RNaseA and then purified using the Qiagen PCR purification kit according to the manufacturer’s instructions. NimbleGen Human Gene Expression array was purchased from Roche Applied Sciences. cDNA samples were labeled, Cy3 hybridized, and processed at the FSU NimbleGen Microarray Facility at Florida State University.

Dataset Information

Effect of Sec61 inhibitor mycolactone on the proteome of the MED17.11 neuronal cell line

Publications

Proteomics Reveals Scope of Mycolactone-mediated Sec61 Blockade and Distinctive Stress Signature.

Similar Datasets

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