CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein Journal Article
| Authors: | Zhang, Y.; Morrone, G.; Zhang, J.; Chen, X.; Lu, X.; Ma, L.; Moore, M.; Zhou, P. |
| Article Title: | CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein |
| Abstract: | The HOXA9 homeodomain protein is a key regulator of hematopoiesis and embryonic development. HOXA9 is expressed in primitive hematopoietic cells, and its prompt downregulation is associated with myelocytic maturation. Although transcriptional inactivation of HOXA9 during hematopoietic differentiation has been established, little is known about the biochemical mechanisms underlying the subsequent removal of HOXA9 protein. Here we report that the CUL-4A ubiquitylation machinery controls the stability of HOXA9 by promoting its ubiquitylation and proteasome-dependent degradation. The homeodomain of HOXA9 is responsible for CUL-4A-mediated degradation. Interfering CUL-4A biosynthesis by ectopic expression or by RNA-mediated interference resulted in alterations of the steady-state levels of HOXA9, mirrored by impairment of the ability of 32D myeloid progenitor cells to undergo proper terminal differentiation into granulocytes. These results revealed a novel regulatory mechanism of hematopoiesis by ubiquitin-dependent proteolysis. |
| Keywords: | controlled study; protein expression; unclassified drug; dna binding protein; human cell; ubiquitin; protein domain; protein function; proteasome endopeptidase complex; steady state; embryo; protein degradation; protein stability; embryo development; cell differentiation; homeodomain proteins; correlation analysis; protein synthesis; hematopoiesis; down regulation; molecular biology; multienzyme complexes; protein determination; cullin 4a; cullin proteins; hox protein; regulator protein; two-hybrid system techniques; promyelocyte; rnai; homeodomain; proteolysis; cysteine endopeptidases; hoxa9; granulocyte precursor cells; humans; human; priority journal; article; cul-4a; protein hoxa9 |
| Journal Title: | EMBO Journal |
| Volume: | 22 |
| Issue: | 22 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2003-11-17 |
| Start Page: | 6057 |
| End Page: | 6067 |
| Language: | English |
| DOI: | 10.1093/emboj/cdg577 |
| PUBMED: | 14609952 |
| PROVIDER: | scopus |
| PMCID: | PMC275435 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work