Two-way inhibition of PAX5 transcriptional activity by PAX5::CBFA2T3.

ABSTRACT: PAX5 promotes B-cell differentiation by transcriptional activation of B-lineage-specific genes. Chromosomal rearrangements in PAX5 account for 2-3% of B-ALL cases, and most lead to the expression of in-frame fusion transcripts. These fusions can encode chimeric proteins composed of the N-terminal portion of PAX5 and the C-terminal region of a variety of heterogeneous fusion partners. We analyzed the function of PAX5::CBFA2T3 (PAX5-C), a fusion protein found in B-cell acute lymphoblastic leukemia. PAX5-C strongly repressed PAX5 transcriptional activity in luciferase assays. In co-immunoprecipitation assays, PAX5-C bound to PAX5 and HDAC1/3. However, neither HDAC knockdown nor treatment with a HDAC inhibitor showed any effect on the repression of PAX5 transactivity by PAX5-C. In addition, PA

SUBMITTER: Ueno R 

PROVIDER: S-EPMC12582980 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature