Resumen de Regulation mechanisms for the heterodimeric transcription factor, PEBP2/CBF
Members of the new PEBP2 (Polyomavirus Enhancer Binding Protein 2) family of heterodimeric transcriptional regulatory protein are composed of two subunits, a and B. One of the genes encoding the a subunit, AMLl /PEBP2aB, 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 ge ne encoding the B subunit (PEBP2j3/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 Amll / Pebp2aB or Pebp2j3/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 a and B subunits of PEBP2 are indispensable for its in vivo function. However, the heterodimerization of the a and B 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.
