Description
Transcripts of the KRAS locus are alternatively spliced to generate two proteins, KRAS4A and KRAS4B, that 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 found 24 and 10 proteins that interact specifically with KRAS4A or KRAS4B, respectively. The KRAS interacting protein most specific to KRAS4A was BIRC6, a large member of the inhibitor of apoptosis protein family unique in possessing E2/E3 ubiquitin ligase activity. We found 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 diminished GTP-loading of and growth stimulation by KRAS4A but not KRAS4B. Thus, BIRC6 is a ubiquitin ligase that inhibits apoptosis and also modifies KRAS4A.
The mass spectrometry files for figures 1D, 1E, S1B, S1C, Supplemental figure 4A are included here.
[doi:10.25345/C5GB1XV3H]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: KRAS4A ; proximity labeling ; BIRC6 ; DatasetType:Proteomics
Contact
Principal Investigators:
(in alphabetical order)
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Beatrix Ueberheide, NYU Langone Grossman School of Medicine, USA
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Trixi
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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis
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