PMID- 10207087
OWN - NLM
STAT- MEDLINE
DCOM- 19990518
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 5
DP  - 1999 May
TI  - Functional and physical interactions between AML1 proteins and an ETS protein,
      MEF: implications for the pathogenesis of t(8;21)-positive leukemias.
PG  - 3635-44
AB  - The AML1 and ETS families of transcription factors play critical roles in
      hematopoiesis; AML1, and its non-DNA-binding heterodimer partner CBFbeta, are
      essential for the development of definitive hematopoiesis in mice, whereas the
      absence of certain ETS proteins creates specific defects in lymphopoiesis or
      myelopoiesis. The promoter activities of numerous genes expressed in
      hematopoietic cells are regulated by AML1 proteins or ETS proteins. MEF (for
      myeloid ELF-1-like factor) is a recently cloned ETS family member that, like
      AML1B, can strongly transactivate several of these promoters, which led us to
      examine whether MEF functionally or physically interacts with AML1 proteins. In
      this study, we demonstrate direct interactions between MEF and AML1 proteins,
      including the AML1/ETO fusion protein, in t(8;21)-positive acute myeloid leukemia
      (AML) cells. Using mutational analysis, we identified a novel ETS-interacting
      subdomain (EID) in the C-terminal portion of the Runt homology domain (RHD) in
      AML1 proteins and determined that the N-terminal region of MEF was responsible
      for its interaction with AML1. MEF and AML1B synergistically transactivated an
      interleukin 3 promoter reporter gene construct, yet the activating activity of
      MEF was abolished when MEF was coexpressed with AML1/ETO. The repression by
      AML1/ETO was independent of DNA binding but depended on its ability to interact
      with MEF, suggesting that AML1/ETO can repress genes not normally regulated by
      AML1 via protein-protein interactions. Interference with MEF function by AML1/ETO
      may lead to dysregulation of genes important for myeloid differentiation, thereby
      contributing to the pathogenesis of t(8;21) AML.
FAU - Mao, S
AU  - Mao S
AD  - Laboratory of Molecular Aspects of Hematopoiesis, Department of Medicine,
      Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
FAU - Frank, R C
AU  - Frank RC
FAU - Zhang, J
AU  - Zhang J
FAU - Miyazaki, Y
AU  - Miyazaki Y
FAU - Nimer, S D
AU  - Nimer SD
LA  - eng
GR  - R01 DK052208/DK/NIDDK NIH HHS/United States
GR  - DK52208/DK/NIDDK NIH HHS/United States
GR  - DK43025/DK/NIDDK NIH HHS/United States
GR  - R56 DK052208/DK/NIDDK NIH HHS/United States
GR  - CA70388/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Elf4 protein, mouse)
RN  - 0 (Interleukin-3)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Amino Acid Sequence
MH  - Core Binding Factor Alpha 2 Subunit
MH  - DNA-Binding Proteins/*metabolism
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Genes, Reporter/genetics
MH  - Hematopoiesis/genetics
MH  - Interleukin-3/genetics
MH  - Leukemia, Myeloid, Acute/*genetics
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - *Proto-Oncogene Proteins
MH  - Recombinant Fusion Proteins/genetics
MH  - Repressor Proteins/genetics
MH  - Transcription Factors/*genetics/*metabolism
MH  - Transfection
MH  - Translocation, Genetic/genetics
MH  - Tumor Cells, Cultured
PMC - PMC84165
EDAT- 1999/04/17 00:00
MHDA- 1999/04/17 00:01
CRDT- 1999/04/17 00:00
PHST- 1999/04/17 00:00 [pubmed]
PHST- 1999/04/17 00:01 [medline]
PHST- 1999/04/17 00:00 [entrez]
AID - 10.1128/mcb.19.5.3635 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 May;19(5):3635-44. doi: 10.1128/mcb.19.5.3635.