|  Help  |  About  |  Contact Us

Publication : Shared and distinct roles mediated through C-terminal subdomains of acute myeloid leukemia/Runt-related transcription factor molecules in murine development.

First Author  Fukushima-Nakase Y Year  2005
Journal  Blood Volume  105
Issue  11 Pages  4298-307
PubMed ID  15713794 Mgi Jnum  J:98965
Mgi Id  MGI:3580918 Doi  10.1182/blood-2004-08-3372
Citation  Fukushima-Nakase Y, et al. (2005) Shared and distinct roles mediated through C-terminal subdomains of acute myeloid leukemia/Runt-related transcription factor molecules in murine development. Blood 105(11):4298-307
abstractText  AML1/Runx1 is a frequent target of human leukemia-associated gene aberration and encodes a transcription factor with nonredundant biologic functions in initial development of definitive hematopoiesis, T-cell development, and steady-state platelet production. AML1/Runx1 and 2 closely related family genes, AML2/Runx3 and AML3/Runx2/Cbfa1, present in mammals, comprise the Runt-domain transcription factor family. Although they have similar structural and biochemical properties, gene-targeting experiments have identified distinct biologic roles. To directly determine the presence of functional overlap among runt-related transcription factor (Runx) family molecules, we replaced the C-terminal portion of acute myeloid leukemia 1 (AML1) with that derived from its family members, which are variable in contrast to conserved Runt domain, using the gene knock-in method. We found that C-terminal portions of either AML2 or AML3 could functionally replace that of AML1 for myeloid development in culture and within the entire mouse. However, while AML2 substituted for AML1 could effectively rescue lymphoid lineages, AML3 could not, resulting in a smaller thymus and lymphoid deficiency in peripheral blood. Substitution by the C-terminal portion of AML3 also led to high infantile mortality and growth retardation, suggesting that AML1 has as yet unidentified effects on these phenotypes. Thus, the C-terminal portions of Runx family members have both similar and distinct biologic functions.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

7 Bio Entities

Trail: Publication

0 Expression