Year: 2003
Type: article
Abstract: Core-binding factors (CBFs) are a small family of heterodimeric transcription factors that play critical roles in hematopoiesis and in the development of bone, stomach epithelium, and proprioceptive neurons. Mutations in CBF genes are found in leukemias, bone disorders, and gastric cancer. CBFs consist of a DNA-binding CBF alpha subunit and a non-DNA-binding CBF beta subunit. DNA binding and heterodimerization with CBF beta are mediated by the Runt domain in CBF alpha. Here we report an alanine-scanning mutagenesis study of the Runt domain that targeted amino acids identified by structural studies to reside at the DNA or CBF beta interface, as well as amino acids mutated in human disease. We determined the energy contributed by each of the DNA-contacting residues in the Runt domain to DNA binding both in the absence and presence of CBF beta. We propose mechanisms by which mutations in the Runt domain found in hematopoietic and bone disorders affect its affinity for DNA.
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Awards: Structure/Function of CBFbeta, G2220559029, Biochemistry of Leukemia Virus Core Binding Factor, G3603032296, NMR STRUCTURAL STUDIES OF CBFA RUNT DOMAIN DNA COMPLEX, G4352452541, MOUSE MODELS FOR FAMILIAL PLATELET DISORDER, NMR STRUCTURAL STUDIES OF CORE BINDING FACTOR, G5320994986, G5653539124, G8040906280
OpenAlex ID: W1974362197