Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia.
Oncogenic conversion of transcription factors by chromosomal translocations is implicated in leukemogenesis. We report that the t(17;19) in acute lymphoblastic leukemia produces a chimeric transcription factor consisting of the amino-terminal portion of HLH proteins E12/E47 (products of the E2A gene) fused to the basic DNA-binding and leucine zipper dimerization motifs of a novel hepatic protein called hepatic leukemia factor (Hlf). Hlf, which is not normally transcribed in lymphoid cells, belongs to the recently described PAR subfamily of basic leucine zipper (bZIP) proteins, which also includes Dbp and Tef/Vbp. Wild-type Hlf is able to bind DNA specifically as a homodimer or as a heterodimer with other PAR factors. Structural alterations of the E2a-Hlf fusion protein markedly impair its ability to bind DNA as a homodimer compared with wild-type Hlf. However, E2a-Hlf can bind DNA as a heterodimer with other PAR proteins, suggesting a novel mechanism for leukemogenic conversion of a bZIP transcription factor.
Hunger
S P
SP
Department of Pathology, Stanford University School of Medicine, California 94305.
Ohyashiki
K
K
Toyama
K
K
Cleary
M L
ML
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002886:Chromosomes, Human, Pair 17; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C076554:E2a-Hlf fusion protein, human; D015514:Oncogene Proteins, Fusion; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors