AML1-ETO interacts with Sp1 and antagonizes Sp1 transactivity through RUNT domain.
AML1-ETO fusion protein is observed in approximately 12% of acute myeloid leukemia. In the present research, we found that AML1-ETO is able to inhibit Sp1 transactivity. We also found that this inhibition of Sp1 transactivity by AML1-ETO is achieved by interaction between Sp1 and RUNT domain of AML1. AML1b is able to abrogate the inhibition of AML1-ETO. Since Sp1 is involved in hematopoietic cell differentiation, we proposed that AML1-ETO promotes leukemogenesis by blocking cell differentiation through inhibition of Sp1 transactivity.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, PR China.
Hui
H
Wei
Xiangrong
X
Liu
Xiujuan
X
Xiong
Yang
Y
Wang
Qing
Q
Rao
Min
M
Wang
Jianxiang
J
Wang
D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D019891:Leukopoiesis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D000075142:RUNX1 Translocation Partner 1 Protein; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; D016329:Sp1 Transcription Factor