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Systematic Characterization of Mutations Altering Protein Degradation in Human Cancers

ABSTRACT: The Ubiquitin-Proteasome System (UPS) is the primary route for selective protein degradation in human cells. We implicate transcription factors as important substrates. By developing a deep learning model (deepDegron) to identify mutations that result in degron loss, and experimentally validated predictions that gain-of-function truncating mutations in GATA3 result in increased protein stability. We profiled the DNA binding by ChIP-seq of GATA3 in response to point mutations of the implicated degron. We found an increase in DNA binding, with up-regulating peaks preferentially found near estrogen signaling related genes. To serve as control, we include GATA3 with a c-terminal FLAG-tag that would stabilize GATA3 regardless of mutation status. No significant enrichment was observed in the control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162003 | GEO | 2021/01/31

REPOSITORIES: GEO

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