Science Advances· 2026Q1
Comprehensive degron mapping in human transcription factors
- 8citations
- Q1SCImago
- 2026year
Short summary
Researchers mapped degrons in all 1,626 human transcription factors, identifying thousands of known and novel motifs that regulate protein abundance, with mutations linked to melanoma exposing buried degrons.
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Key points
- Mapped degrons in all 1,626 human transcription factors.
- Identified thousands of known and novel degrons.
- Degrons in exposed/disordered regions regulate transcription factor abundance.
- Melanoma mutations expose buried degrons in zinc fingers.
- Variant effects correlate with degron potency.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Gene expression is regulated by the targeted degradation of transcription factors through the ubiquitin-proteasome system. Transcription factors destined for degradation are recognized by E3 ubiquitin-protein ligases through short motifs termed degrons, embedded within the sequence. In this study, we systematically map degrons in all 1,626 human transcription factors. We find thousands of both known and previously unidentified degrons and characterize their sequence properties. Degrons placed within exposed and intrinsically disordered regions regulate the cellular abundance of the transcription factors, while the most common somatic mutations that are linked to skin cutaneous melanoma lead to unfolding and exposure of a buried degron in zinc fingers. We present examples of compartment specific degrons and demonstrate that variant effects in transcription factors correlate with degron potency. Finally, we show that while >60% of all predicted transcriptional activation domains overlap with strong degrons, acidic residues within the remaining transactivating regions counter the degron potency.
The authors' abstract, as published at the source. Science Advances, 2026 · DOI ↗
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Field: Molecular Biology
Molecular BiologyBiochemistry, Genetics and Molecular Biology