Post-Translational Modifications of the DUX4 Protein Impact Toxic Function in FSHD Cell Models.

ABSTRACT:

Objective

Facioscapulohumeral muscular dystrophy (FSHD) is caused by abnormal de-repression of the myotoxic transcription factor DUX4. Although the transcriptional targets of DUX4 are known, the regulation of DUX4 protein and the molecular consequences of this regulation are unclear. Here, we used in vitro models of FSHD to identify and characterize DUX4 post-translational modifications (PTMs) and their impact on the toxic function of DUX4.

Methods

We immunoprecipitated DUX4 protein and performed mass spectrometry to identify PTMs. We then characterized DUX4 PTMs and potential enzyme modifiers using mutagenesis, proteomics, and biochemical assays in HEK293 and human myoblast cell lines.

Results

We identified 17 DUX4 amino acids with PTMs, and generated 55 DUX4 mutants

SUBMITTER: Knox RN 

PROVIDER: S-EPMC10777487 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature