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Ubiquitin Proteomics Analysis of Systemic Sclerosis Lung Fibroblasts with or without KLHL42 knockdown

ABSTRACT: Systemic scleroderma (SSc) is an autoimmune disease which results in fibrotic production in the lung. Resultant SSC-pulmonary fibrosis is the main cause of mortality among SSc patients. From high throughput RNAi screening, we uncovered the ubiquitin E3 ligase KLHL42 as a potential pro-fibrotic mediator of TGFb-dependent fibrotic signaling in primary SSc lung fibroblasts. In this analysis, we sought to uncover putative substrates for KLHL42 by comparing SSc lung fibroblasts with control or KLHL42 siRNA prior to TGFb-treatment, lysis, and TUBE precipitation. The resultant pull-down was analyzed with LC-MS/MS.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Bill Chen

PROVIDER: MSV000084800 | MassIVE | Tue Jan 14 05:30:00 GMT 2020

REPOSITORIES: MassIVE

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Kelch-like protein 42 is a profibrotic ubiquitin E3 ligase involved in systemic sclerosis.

Lear Travis B TB Lockwood Karina C KC Larsen Mads M Tuncer Ferhan F Kennerdell Jason R JR Morse Christina C Valenzi Eleanor E Tabib Tracy T Jurczak Michael J MJ Kass Daniel J DJ Evankovich John W JW Finkel Toren T Lafyatis Robert R Liu Yuan Y Chen Bill B BB

The Journal of biological chemistry 20200217 13

Systemic scleroderma (SSc) is an autoimmune disease that affects over 2.5 million people globally. SSc results in dysfunctional connective tissues with excessive profibrotic signaling, affecting skin, cardiovascular, and particularly lung tissue. Over three-quarters of individuals with SSc develop pulmonary fibrosis within 5 years, the main cause of SSc mortality. No approved medicines to manage lung SSc currently exist. Recent research suggests that profibrotic signaling by transforming growth ...[more]

PMID: 32071084

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