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Baculoviral IAP repeat-containing protein 6 Ubiquitinates KRAS4A

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Eclipse, timsTOF HT, Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Beatrix Ueberheide

PROVIDER: MSV000096322 | MassIVE | Wed Nov 06 16:06:00 GMT 2024

SECONDARY ACCESSION(S): PXD057589

REPOSITORIES: MassIVE

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