Proximity map for p53 unveils a strong link with PML Nuclear Bodies in HEK293 cells

Abstract

The tumor suppressor p53 is among the most studied proteins in cancer, with mutations in nearly half of all tumors. Even when TP53 is intact, its regulatory pathways are often disrupted, underscoring its central role in tumorigenesis. To explore how cellular context shapes the subcellular environment of p53, we used BioID proximity labeling in HEK293 cells. These experiments revealed a striking enrichment of proteins involved in SUMOylation and proteins that reside in PML nuclear bodies. A strong enrichment of the adenoviral E1B protein, originally used for transformation of this cell line, may explain this striking observation, and can shed light on the remarkable difference with the proximity map of p53 in the HCT116 colon carcinoma cell line. Strong enrichment of the mediator complex in HCT116, related to active p53-dependent transcription, is missing in 293 cells and can explain the lack of p53 transcriptional activity in these cells. This study emphasizes how cellular transformation can affect the proximal proteome of a key protein in cell cycle control, DNA repair, apoptosis, senescence and metabolism, and confirms previously reported inhibition of p53-dependent transcription by sequestering the protein in PML nuclear bodies.