PMID- 10082572
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 4
DP  - 1999 Apr
TI  - HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells.
PG  - 3051-61
AB  - Aberrant activation of the HOX, MEIS, and PBX homeodomain protein families is
      associated with leukemias, and retrovirally driven coexpression of HOXA9 and
      MEIS1 is sufficient to induce myeloid leukemia in mice. Previous studies have
      demonstrated that HOX-9 and HOX-10 paralog proteins are unique among HOX
      homeodomain proteins in their capacity to form in vitro cooperative DNA binding
      complexes with either the PBX or MEIS protein. Furthermore, PBX and MEIS proteins
      have been shown to form in vivo heterodimeric DNA binding complexes with each
      other. We now show that in vitro DNA site selection for MEIS1 in the presence of 
      HOXA9 and PBX yields a consensus PBX-HOXA9 site. MEIS1 enhances in vitro
      HOXA9-PBX protein complex formation in the absence of DNA and forms a trimeric
      electrophoretic mobility shift assay (EMSA) complex with these proteins on an
      oligonucleotide containing a PBX-HOXA9 site. Myeloid cell nuclear extracts
      produce EMSA complexes which appear to contain HOXA9, PBX2, and MEIS1, while
      immunoprecipitation of HOXA9 from these extracts results in coprecipitation of
      PBX2 and MEIS1. In myeloid cells, HOXA9, MEIS1, and PBX2 are all strongly
      expressed in the nucleus, where a portion of their signals are colocalized within
      nuclear speckles. However, cotransfection of HOXA9 and PBX2 with or without MEIS1
      minimally influences transcription of a reporter gene containing multiple
      PBX-HOXA9 binding sites. Taken together, these data suggest that in myeloid
      leukemia cells MEIS1 forms trimeric complexes with PBX and HOXA9, which in turn
      can bind to consensus PBX-HOXA9 DNA targets.
FAU - Shen, W F
AU  - Shen WF
AD  - Departments of Medicine, University of California VA Medical Center, San
      Francisco, California, USA. largman@cgl.ucsf.edu
FAU - Rozenfeld, S
AU  - Rozenfeld S
FAU - Kwong, A
AU  - Kwong A
FAU - Kom ves, L G
AU  - Kom ves LG
FAU - Lawrence, H J
AU  - Lawrence HJ
FAU - Largman, C
AU  - Largman C
LA  - eng
GR  - R01 DK048642/DK/NIDDK NIH HHS/United States
GR  - DK48642/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
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 (Homeodomain Proteins)
RN  - 0 (MEIS1 protein, human)
RN  - 0 (Meis1 protein, mouse)
RN  - 0 (Myeloid Ecotropic Viral Integration Site 1 Protein)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PBX2 protein, human)
RN  - 0 (Pbx2 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (homeobox protein HOXA9)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Bone Marrow Cells/*metabolism
MH  - Cell Nucleus/metabolism/ultrastructure
MH  - Dimerization
MH  - Homeodomain Proteins/*metabolism
MH  - Humans
MH  - Leukemia, Myeloid/pathology
MH  - Mice
MH  - Myeloid Ecotropic Viral Integration Site 1 Protein
MH  - Neoplasm Proteins/*metabolism
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Subcellular Fractions/metabolism
MH  - Transcription Factors
MH  - Transcription, Genetic
MH  - U937 Cells
PMC - PMC84099
EDAT- 1999/03/19 00:00
MHDA- 1999/03/19 00:01
CRDT- 1999/03/19 00:00
PHST- 1999/03/19 00:00 [pubmed]
PHST- 1999/03/19 00:01 [medline]
PHST- 1999/03/19 00:00 [entrez]
AID - 10.1128/mcb.19.4.3051 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Apr;19(4):3051-61. doi: 10.1128/mcb.19.4.3051.