Miz-1 regulates translation of Trp53 via ribosomal protein L22 in cells undergoing V(D)J recombination.
basic_science · Level V
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- Record sourced from PubMed, PMID 25468973.
- Also identified by DOI 10.1073/pnas.1412107111 and PMC identifier 4273400.
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Abstract
To be effective, the adaptive immune response requires a large repertoire of antigen receptors, which are generated through V(D)J recombination in lymphoid precursors. These precursors must be protected from DNA damage-induced cell death, however, because V(D)J recombination generates double-strand breaks and may activate p53. Here we show that the BTB/POZ domain protein Miz-1 restricts p53-dependent induction of apoptosis in both pro-B and DN3a pre-T cells that actively rearrange antigen receptor genes. Miz-1 exerts this function by directly activating the gene for ribosomal protein L22 (Rpl22), which binds to p53 mRNA and negatively regulates its translation. This mechanism limits p53 expression levels and thus contains its apoptosis-inducing functions in lymphocytes, precisely at differentiation stages in which V(D)J recombination occurs.
Medical subject headings
- Gene Expression Regulation
- Lymphoid Progenitor Cells
- Nuclear Proteins
- Protein Biosynthesis
- Protein Inhibitors of Activated STAT
- RNA-Binding Proteins
- Ribosomal Proteins
- Tumor Suppressor Protein p53
- V(D)J Recombination