Regulation of GATA-binding protein 2 levels via ubiquitin-dependent degradation by Fbw7: involvement of cyclin B-cyclin-dependent kinase 1-mediated phosphorylation of THR176 in GATA-binding protein 2.

摘要: A GATA family transcription factor, GATA-binding protein 2 (GATA2), participates in cell growth and differentiation of various cells, such as hematopoietic stem cells. Although its expression level is controlled by transcriptional induction proteolytic degradation, the responsible E3 ligase has not been identified. Here, we demonstrate that F-box/WD repeat-containing 7 (Fbw7/Fbxw7), a component Skp1, Cullin 1, F-box-containing complex (SCF)-type ligase, an for GATA2. GATA2 contains division control 4 (Cdc4) phosphodegron (CPD), consensus motif ubiquitylation Fbw7, which includes Thr176. Ectopic Fbw7 destabilized promoted proteasomal degradation. Substitution threonine 176 to alanine inhibited binding with degradation was suppressed. The CPD kinase, mediates phosphorylation Thr176, cyclin B-cyclin-dependent kinase 1 (CDK1). Moreover, depletion endogenous stabilized K562 Conditional mice increased levels cells myeloid progenitors at early stage. Increased Fbw7-conditional knock-out were correlated decrease c-Kit high expressing population progenitor Our results suggest bona fide ubiquitin vivo.