Regulation mechanisms for the heterodimeric transcription factor, PEBP2/CBF

Abstract

Members of the new PEBP2 (Polyomavirus Enhancer Binding Protein 2) family of heterodimeric transcriptional regulatory protein are composed of two subunits, α and β. One of the genes encoding the α subunit, AML/IPEBP2aB, was identified at the breakpoints of various chromosome translocations, including t(8;21) and t(12;21) associated with acute myeloid leukemia and acute lymphoblastic leukemia, respectively. The gene encoding the β subunit (PEBP2β/CBFB) was also shown to be the target of the inversion of chromosome 16, another chromosomal anomaly associated with acute myeloid leukemia. Targeted disruption of either the Aml1/Pebp2αβ or Pebp2β/Cbfb gene resulted in strikingly similar phenotypes such as lack of definitive hematopoiesis of the fetal liver and accompanying hemorrhage of the central nervous system. These observations suggest that both α and β subunits of PEBP2 are indispensable for its in vivo function. However, the heterodimerization of the α and β subunit does not seem to occur readily suggesting that their capacity to associate might be an important rate limiting step in PEBP2 site-dependent transcription regulation. In this review, we concentrate on the possible regulatory mechanisms of PEBP2 activity in relation to leukemogenesis.