The polyomavirus enhancer binding protein 2 (PEBP2) or core binding factor
(CBF) is a heterodimeric enhancer binding protein that is associated with g
enetic regulation of hematopoiesis and osteogenesis. Aberrant forms of PEBP
2/CBF are implicated in the cause of the acute human leukemias and in a dis
order of bone development known as cleidocranial dysplasia. The common deno
minator in the natural and mutant forms of this protein is a highly conserv
ed domain of PEBP2/CBF alpha, termed the Runt domain (RD), which is respons
ible for both DNA binding and heterodimerization with the beta subunit of P
EBP2/CBF. The three-dimensional structure of the RD bound to DNA has been d
etermined to be an S-type immunoglobulin fold, establishing a structural re
lationship between the RD and the core DNA binding domains of NF-kappa B, N
FAT1, p53 and the STAT proteins, NMR spectroscopy of a 43.6 kD RD-beta-DNA
ternary complex identified the surface of the RD in contact with the beta s
ubunit, suggesting a mechanism for the enhancement of RD DNA binding by bet
a. Analysis of leukemogenic mutants within the RD provides molecular insigh
ts into the role of this factor in leukemogenesis and cleidocranial dysplas
ia.