Deciphering the ghost proteome in ovarian cancer cells by deep proteogenomic characterization.

ABSTRACT: Proteogenomics is becoming a powerful tool in personalized medicine by linking genomics, transcriptomics, and mass spectrometry (MS)-based proteomics. Due to increasing evidence of alternative open reading frame-encoded proteins (AltProts), proteogenomics has high potential to unravel the characteristics, variants, and expression levels of the alternative proteome in cells. To characterize a broader view of the proteome of ovarian cancer cells compared to ovarian epithelial cells, cell-specific RNA-sequencing databases were generated.128 reference proteins (RefProts) and 30 AltProts were identified exclusively shared by SKOV-3 and PEO-4. Among them, an AltProt variant of IP_715944 was identified mutated (Leu44Pro) and translated from DHX8. Additionally, the abundance level of the proteome was assessed, finding specific expression variation of RefProts and AltProts in different subcellular compartments. The identification of 117 RefProt and two AltProt variants was highlighted, along with their possible implications in the different physio-pathological characteristics. To identify the possible involvement of AltProts in cellular processes, crosslinking-MS (XL-MS) was performed in each cell line to identify AltProt-RefProt protein-protein interactions. An interaction of POLD3 and the AltProt IP_183088 was identified, which after molecular docking was placed between POLD3-POLD2 binding sites highlighting the possibility of the involvement of IP_183088 in the cellular processes of DNA replication and repair.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Ovarian Cancer

SUBMITTER: Diego Fernando Garcia del Rio  

LAB HEAD: Michel Salzet

PROVIDER: PXD045689 | Pride | 2025-05-06

REPOSITORIES: Pride