Defective erythropoiesis in a mouse model of reduced Fbxo7 expression due to decreased p27 expression.

ABSTRACT: During the final stages of erythropoiesis, lineage-restricted progenitors mature over three to five cell divisions, culminating with withdrawal from the cell cycle and the loss of most organelles, including mitochondria and nuclei. Recent genome-wide association studies in human populations have associated several SNPs near or within FBXO7 with erythrocyte phenotypes. Fbxo7 encodes a multi-functional F-box protein known to bind p27 and participate in selective mitophagy. One SNP causes an amino acid substitution (Met115Ile) and is associated with smaller erythrocytes. We find that the less common IIe115 allele of Fbxo7 binds less efficiently to p27, and cells expressing this allele proliferate faster than cells expressing Met115. We show that an erythroleukaemic cell line with reduced Fbxo

SUBMITTER: Randle SJ 

PROVIDER: S-EPMC4583784 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature