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J Immunol. 2001 Apr 15;166(8):5058-67.

Identification of novel functional regions important for the activity of HOXB7 in mammalian cells.

Author information

1
Division of Hematology-Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, University of California School of Medicine, Los Angeles, CA 90095, USA.

Abstract

Members of the HOX family of homeobox transcription factors play a role in pattern formation in diverse developmental systems. The clearly documented role of HOX genes in the proliferation and differentiation of primary hematopoietic cells and cell lines provides a convenient system to pursue a biochemical analysis of HOX gene function in mammalian cells. To explore the role of HOXB7 in myeloid hematopoiesis, a number of mutations and deletions in the gene were constructed that targeted sequences with known functions or in regions that had not been examined previously. The wild-type and mutant B7 constructs were introduced into the murine myelomonocytic cell line, 32D, and assayed for their effects on G-CSF-induced myeloid differentiation. Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this effect. Interestingly, mutations eliminating two target sites for casein kinase II, the glutamate-rich C terminus, or the first 14 amino acids of HOXB7, led to enhanced 32D differentiation. A model proposing a role for these regions of HOXB7 is presented.

PMID:
11290787
DOI:
10.4049/jimmunol.166.8.5058
[Indexed for MEDLINE]
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