Functional characterization of TEL/AML1 fusion protein in the regulation of human CR1 gene promoter.
The TEL/AML1 fusion gene occurs in childhood B-cell acute lymphoblastic leukemia (ALL) as a result of the translocation of human chromosome 12;21. Using reporter gene assays, we have functionally characterized TEL, AML1 and TEL/AML1 fusion proteins in the regulation of the human CR1 gene. Analysis of transcription activities showed that AML1 increased the CR1 promoter activity and that TEL repressed the basal activity of the promoter. Increased activities of the CR1 promoter by AML1 protein were reduced by the TEL protein in a concentration-dependent manner. When TEL/AML1 and AML1 proteins are present in cells at the same time, the TEL/AML1 protein inhibits the transactivation activities of AML1 protein on the human CR1 promoter even though TEL/AML1 retains the transactivation domain of AML1. A mutation analysis of the human CR1 promoter revealed that the binding sites for TEL and AML1 are necessary for the action of TEL and TEL/AML1, respectively. Thus, production of the TEL/AML1 protein by translocation of human chromosome 12;21 may contribute to leukemogenesis by the specific inhibition of AML1-dependent activation of myeloid promoters.
Song
H
H
School of Life Sciences and Research Institute for Genetic Engineering, Chungbuk National University, Cheongju, Korea.
Kim
J H
JH
Rho
J K
JK
Park
S Y
SY
Kim
C G
CG
Choe
S Y
SY
D001665:Binding Sites; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000648:ultrastructure; D050676:Core Binding Factor Alpha 2 Subunit; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011951:Receptors, Complement / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011951:Receptors, Complement; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein