Proteomics,Multiomics

Dataset Information

0

Protein quality control by MARCH6/TRC8


ABSTRACT: Forward genetic screens in human cells we find that the proteasome-mediated degradation of the soluble misfolded reporter, mCherry-CL1, involves two ER-resident E3 ligases, MARCH6 and TRC8. To identify a more physiological correlate we used quantitative mass spectrometry and found that TRC8 and MARCH6 depletion altered the turnover of the tail-anchored protein Heme-Oxygenase-1 (HO-1).

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: James Williamson  

LAB HEAD: James Nathan

PROVIDER: PXD008955 | Pride | 2018-04-18

REPOSITORIES: Pride

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Publications

MARCH6 and TRC8 facilitate the quality control of cytosolic and tail-anchored proteins.

Stefanovic-Barrett Sandra S   Dickson Anna S AS   Burr Stephen P SP   Williamson James C JC   Lobb Ian T IT   van den Boomen Dick Jh DJ   Lehner Paul J PJ   Nathan James A JA  

EMBO reports 20180308 5


Misfolded or damaged proteins are typically targeted for destruction by proteasome-mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome-mediated degradation of the soluble misfolded reporter, mCherry-CL1, involves two ER-resident E3 ligases, MARCH6 and TRC8. mCherry-CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with comp  ...[more]

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