Regulation mechanisms for the heterodimeric transcription factor, PEBP2/CBF

S-C. Bae1 and Y. Ito2

1Department of Biochemistry, School of Medicine, Chungbuk National University, Chungju, Korea and 2 Department of Cell Regulation Institute for Virus Research, Kyoto University Sakyo-ku, Kyoto, Japan

Offprint requests to: S-C. Bae Ph.D., Department of Biochemistry, School of Medicine, Chungbuk National University, Chungju, 360-763, Korea. e-mail: scbae@med.chungbuk.ac.kr

Summary. Members of the new PEBP2 (Polyomavirus Enhancer Binding Protein 2) family of heterodimeric transcriptional regulatory protein are composed of two subunits, a and ß. One of the genes encoding the a subunit, AML1/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 gene encoding the ß subunit (PEBP2ß/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/Pebp2aB or Pebp2ß/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 ß subunits of PEBP2 are indispensable for its in vivo function. However, the heterodimerization of the a and ß 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. Histol. Histopathol. 14, 1213-1221 (1999)

Key words: PEBP2, CBF, AML1, Hematopoiesis, Leukemia


DOI: 10.14670/HH-14.1213