FEBS Letters
Volume 582, Issue 15 , Pages 2167-2172, 25 June 2008

AML1-ETO interacts with Sp1 and antagonizes Sp1 transactivity through RUNT domain

Edited by Gianni Cesareni

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 300020, PR China

Received 3 March 2008; received in revised form 16 May 2008; accepted 20 May 2008. published online 03 June 2008.

Abstract 

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.

Structured summary


MINT-6549474: AML1-ETO (genbank_protein_gi:AAB34820) physically interacts (MI:0218) with Sp1 (uniprotkb:P08047) by anti bait coimmunoprecipitation (MI:0006)

MINT-6549439: Sp1 (uniprotkb:P08047) physically interacts (MI:0218) with AML1-ETO (uniprotkb:AAB34820) by anti tag coimmunoprecipitation (MI:0007)

MINT-6549458: Sp1 (uniprotkb:P08047) physically interacts (MI:0218) with AML1a (uniprotkb:Q01196-2) by anti tag coimmunoprecipitation (MI:0007)

Abbreviations: PB, phenylbutyrate, HCK, human hematopoietic cell kinase, AML, Acute myeloid leukemia

Keywords: AML1-ETO, Sp1, Cell differentiation, Acute myeloid leukemia, Transcription regulation

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PII: S0014-5793(08)00454-7

doi:10.1016/j.febslet.2008.05.030

FEBS Letters
Volume 582, Issue 15 , Pages 2167-2172, 25 June 2008