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

FEBS Lett. 2008 Jun 25;582(15):2167-72. doi: 10.1016/j.febslet.2008.05.030. Epub 2008 Jun 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Leukopoiesis / genetics*
  • Oncogene Proteins, Fusion / metabolism*
  • Protein Structure, Tertiary
  • RUNX1 Translocation Partner 1 Protein
  • Sp1 Transcription Factor / antagonists & inhibitors*
  • Sp1 Transcription Factor / metabolism
  • Transcriptional Activation*

Substances

  • AML1-ETO fusion protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein
  • RUNX1 protein, human
  • Sp1 Transcription Factor