A truncated and catalytically inactive form of KDM5B histone demethylase accumulates in breast cancer cells and regulates H3K4 tri-methylation and gene expression

ABSTRACT: KDM5B histone demethylase is overexpressed in many cancers with an ambivalent role in oncogenesis which depends on the specific contest. A putative explanation of this ambivalence could be represented by the expression pattern of different protein isoforms with different functional roles which could be present at different levels in different cancer cell lines. We show here that one of these isoforms (NTT) accumulates in breast cancer cell lines up to 50-60% of the total, due to a remarkable protein stability relative to the canonical PLU-1 isoform which shows a much faster turnover. Mass Spectrometry (MS) profiling of histone post-translational modifications showed that overexpression of this isoform in MCF7 cells leads to an increase in H3K4 trimethylation. We discuss the relevance of this finding at the light of the hypothesis that KDM5B may possess regulatory roles independent of its catalytic activity.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Breast, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Giulia Robusti  

LAB HEAD: Tiziana Bonaldi

PROVIDER: PXD033337 | Pride | 2023-07-20

REPOSITORIES: Pride