Fbw7-dependent cyclin E regulation ensures terminal maturation of bone marrow erythroid cells by restraining oxidative metabolism.

ABSTRACT: The mechanisms that coordinate the final mitotic divisions of terminally differentiated bone marrow (BM) erythroid cells with components of their structural and functional maturation program remain largely undefined. We previously identified phenotypes resembling those found in early-stage myelodysplastic syndromes (MDS), including ineffective erythropoiesis, morphologic dysplasia and BM hyper-cellularity, in a knock-in mouse model in which cyclin E mutations were introduced at its two Cdc4 phosphodegrons (CPDs) to ablate Fbw7-dependent ubiquitination and degradation. Here, we have examined the physiologic consequences of cyclin E dysregulation in BM erythroid cells during terminal maturation in vivo. We found that cyclin E protein levels in BM erythroid cells are dynamically regulated in

SUBMITTER: Xu Y 

PROVIDER: S-EPMC3939062 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature