Reduced EIF6 dosage attenuates TP53 activation in models of Shwachman-Diamond syndrome.

ABSTRACT: Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency, and bony abnormalities with an increased risk of myeloid neoplasia. Almost all cases of SDS result from biallelic mutations in Shwachman-Bodian-Diamond syndrome (SBDS). SBDS interacts with elongation factor-like 1 (EFL1) to displace eukaryotic initiation factor 6 (EIF6) from the 60S ribosomal subunit. Released EIF6 permits the assembly of ribosomal large and small subunits in the cytoplasm. Decreased EIF6 levels due to haploinsufficiency or missense mutations, which lead to decreased protein expression, may provide a somatic genetic rescue and antileukemic effects. We observed accumulation of EIF6 protein in sbds-KO zebrafish models, confirmed this accumulation in patient-derived tissues, a

SUBMITTER: Oyarbide U 

PROVIDER: S-EPMC11996912 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature