PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31863007.
- Also identified by DOI 10.1038/s41467-019-13608-1 and PMC identifier 6925188.
- 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
p53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is defective as a tumor suppressor. We also find that expressions of PBRM1 and p21 correlate with each other in human kidney cancer samples. Our findings uncover a tumor suppressive mechanism of PBRM1 in kidney cancer and provide a mechanistic insight into the crosstalk between p53 and SWI/SNF complexes.
Medical subject headings
- Cyclin-Dependent Kinase Inhibitor p21
- DNA-Binding Proteins
- Gene Expression Regulation, Neoplastic
- Kidney Neoplasms
- Transcription Factors
- Tumor Suppressor Protein p53