Proteomics

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Simultaneous proteome localization and turnover analysis reveals spatiotemporal coordinations of unfolded protein response


ABSTRACT: The functionality of proteins is dependent on their spatial and temporal distributions, neither of which is directly measured by static protein abundance. Here we report a mass spectrometry-based proteomics workflow and data analysis pipeline, named Simultaneous Proteome Localization and Turnover (SPLAT), to concurrently examine the turnover dynamics and subcellular distributions of whole cell proteomes under perturbation. SPLAT builds on prior work in protein turnover measurements and subcellular localization profiling, by combining dynamic stable isotope labeling, differential ultracentrifugation, and kinetic modeling to concurrently measure changes in protein turnover and subcellular localization under perturbation in one experiment.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Edward Lau 

PROVIDER: PXD038054 | JPOST Repository | Sat Dec 31 00:00:00 GMT 2022

REPOSITORIES: jPOST

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Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions.

Currie Jordan J   Manda Vyshnavi V   Robinson Sean K SK   Lai Celine C   Agnihotri Vertica V   Hidalgo Veronica V   Ludwig R W RW   Zhang Kai K   Pavelka Jay J   Wang Zhao V ZV   Rhee June-Wha JW   Lam Maggie P Y MPY   Lau Edward E  

Nature communications 20240311 1


The spatial and temporal distributions of proteins are critical to protein function, but cannot be directly assessed by measuring protein bundance. Here we describe a mass spectrometry-based proteomics strategy, Simultaneous Proteome Localization and Turnover (SPLAT), to measure concurrently protein turnover rates and subcellular localization in the same experiment. Applying the method, we find that unfolded protein response (UPR) has different effects on protein turnover dependent on their subc  ...[more]

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