Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34526502.
- Also identified by DOI 10.1038/s41467-021-25550-2 and PMC identifier 8443592.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion.
Medical subject headings
- Gene Expression Regulation, Neoplastic
- Neoplasms
- Protein Aggregation, Pathological
- Tumor Suppressor Protein p53