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

Citation
Y. Yaron et al., Identification of novel functional regions important for the activity of HOXB7 in mammalian cells, J IMMUNOL, 166(8), 2001, pp. 5058-5067
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
0022-1767 → ACNP
Volume
166
Issue
8
Year of publication
2001
Pages
5058 - 5067
Database
ISI
SICI code
0022-1767(20010415)166:8<5058:IONFRI>2.0.ZU;2-R
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 hemat opoietic cells and cell lines provides a convenient system to pursue a bioc hemical analysis of HOX gene function in mammalian cells. To explore the ro le of HOXB7 in myeloid hematopoiesis, a number of mutations and deletions i n 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, 32 D, and assayed for their effects on G-CSF-induced myeloid differentiation. Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutatio ns in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this e ffect. Interestingly, mutations eliminating two target sites for casein kin ase II, the glutamate-rich C terminus, or the first 14 amino acids of IIOXB 7, led to enhanced 32D differentiation. A model proposing a role for these regions of HOXB7 is presented. The Journal of Immunology, 2001.