Degron map of all 1,626 human transcription factors reveals thousands of motifs
Researchers mapped protein-degradation motifs across every human transcription factor and linked a buried degron to common melanoma mutations in zinc fingers.
Researchers systematically mapped degrons across all 1,626 human transcription factors, according to a study in Science Advances science.org
Science Advancesscience.orgOpen source ↗. Degrons are short sequence motifs that E3 ubiquitin-protein ligases recognize to target proteins for degradation by the ubiquitin-proteasome system. The screen found thousands of degrons, both known and previously unidentified, and the authors characterized their sequence properties.
Degrons placed within exposed and intrinsically disordered regions regulate the cellular abundance of the transcription factors. The most common somatic mutations linked to skin cutaneous melanoma lead to unfolding of zinc fingers and exposure of a buried degron. The authors also describe compartment-specific degrons and report that variant effects in transcription factors correlate with degron potency.
More than 60% of all predicted transcriptional activation domains overlap with strong degrons. In the remaining transactivating regions, acidic residues counter degron potency, the authors report.
