HLF, A NOVEL HEPATIC BZIP PROTEIN, SHOWS ALTERED DNA-BINDING PROPERTIES FOLLOWING FUSION TO E2A IN T(17-19) ACUTE LYMPHOBLASTIC-LEUKEMIA

HLF, A NOVEL HEPATIC BZIP PROTEIN, SHOWS ALTERED DNA-BINDING PROPERTIES FOLLOWING FUSION TO E2A IN T(17-19) ACUTE LYMPHOBLASTIC-LEUKEMIA
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DOI:
10.1101/gad.6.9.1608
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发表时间:
1992-09-01
影响因子:
10.5
通讯作者:
CLEARY, ML
CLEARY, ML
中科院分区:
生物学1区
文献类型:
--
作者:
HUNGER, SP;OHYASHIKI, K;CLEARY, ML

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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 Tes/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.