ArticleCell reports2025
The differential interactomes of the KRAS splice variants identify BIRC6 as a ubiquitin ligase for KRAS4A.
Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Rewiring KRAS-driven cancers through the ubiquitin-proteasome system: therapeutic opportunities with a focus on deubiquitinase.Experimental & molecular medicine · 2026Review
- The IAP family member BRUCE/BIRC6: an emerging new player in balancing life and death.Apoptosis : an international journal on programmed cell death · 2026Review
- Pancreatic Cells Are Resistant to KRASQ61L Expression due to Hyperactive ERK/MAPK Signaling and Apoptosis Induction.Cancer research communications · 2025Article
- Review
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Authors and funding
15 authors.
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Abstract
Transcripts of the KRAS locus are alternatively spliced to generate two proteins, KRAS4A and KRAS4B, which differ in their membrane-targeting sequences. These splice variants have been conserved for more than 450 million years, suggesting non-overlapping functions driven by differential membrane association. Here, we use proximity labeling to map the differential interactomes of the KRAS splice variants. We find 24 and 10 proteins that interact specifically with KRAS4A or KRAS4B, respectively. The KRAS interacting protein most specific to KRAS4A is BIRC6, a large member of the inhibitor of apoptosis protein family unique in possessing E2/E3 ubiquitin ligase activity. We find that this interaction takes place on the Golgi apparatus and results in the mono- and di-ubiquitination of KRAS4A at lysines 128 and 147. Silencing BIRC6 diminishes GTP loading of and growth stimulation by KRAS4A but not KRAS4B. Thus, BIRC6 is a ubiquitin ligase that inhibits apoptosis and also modifies KRAS4A.
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