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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2000-11-9
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pubmed:abstractText |
The lineage-specific transcription factors GATA-1 and PU.1 can physically interact to inhibit each other's function, but the mechanism of repression of GATA-1 function by PU.1 has not been elucidated. Both the N terminus and the C terminus of PU.1 can physically interact with the C-terminal zinc finger of GATA-1. It is demonstrated that the PU.1 N terminus, but not the C terminus, is required for inhibiting GATA-1 function. Induced overexpression of PU.1 in K562 erythroleukemia cells blocks hemin-induced erythroid differentiation. In this system, PU.1 does not affect the expression of GATA-1 messenger RNA, protein, or nuclear localization. However, GATA-1 DNA binding decreases dramatically. By means of electrophoretic mobility shift assays with purified proteins, it is demonstrated that the N-terminal 70 amino acids of PU.1 can specifically block GATA-1 DNA binding. In addition, PU.1 had a similar effect in the G1ER cell line, in which the GATA-1 null erythroid cell line G1E has been transduced with a GATA-1-estrogen receptor fusion gene, which is directly dependent on induction of the GATA-1 fusion protein to effect erythroid maturation. Consistent with in vitro binding assays, overexpression of PU.1 blocked DNA binding of the GATA-1 fusion protein as well as GATA-1-mediated erythroid differentiation of these G1ER cells. These results demonstrate a novel mechanism by which function of a lineage-specific transcription factor is inhibited by another lineage-restricted factor through direct protein-protein interactions. These findings contribute to understanding how protein-protein interactions participate in hematopoietic differentiation and leukemogenesis. (Blood. 2000;96:2641-2648)
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Erythroid-Specific DNA-Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/GATA1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2641-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11023493-Biological Transport,
pubmed-meshheading:11023493-Cell Differentiation,
pubmed-meshheading:11023493-Cell Lineage,
pubmed-meshheading:11023493-Cell Nucleus,
pubmed-meshheading:11023493-DNA,
pubmed-meshheading:11023493-DNA, Neoplasm,
pubmed-meshheading:11023493-DNA-Binding Proteins,
pubmed-meshheading:11023493-Erythroid Precursor Cells,
pubmed-meshheading:11023493-Erythroid-Specific DNA-Binding Factors,
pubmed-meshheading:11023493-Erythropoiesis,
pubmed-meshheading:11023493-Estradiol,
pubmed-meshheading:11023493-GATA1 Transcription Factor,
pubmed-meshheading:11023493-Gene Expression Regulation, Leukemic,
pubmed-meshheading:11023493-Genes, Synthetic,
pubmed-meshheading:11023493-Humans,
pubmed-meshheading:11023493-K562 Cells,
pubmed-meshheading:11023493-Neoplasm Proteins,
pubmed-meshheading:11023493-Protein Binding,
pubmed-meshheading:11023493-Protein Structure, Tertiary,
pubmed-meshheading:11023493-Proto-Oncogene Proteins,
pubmed-meshheading:11023493-RNA, Messenger,
pubmed-meshheading:11023493-RNA, Neoplasm,
pubmed-meshheading:11023493-Receptors, Estrogen,
pubmed-meshheading:11023493-Recombinant Fusion Proteins,
pubmed-meshheading:11023493-Trans-Activators,
pubmed-meshheading:11023493-Transcription Factors,
pubmed-meshheading:11023493-Transfection
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pubmed:year |
2000
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pubmed:articleTitle |
PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding.
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pubmed:affiliation |
Hematology/Oncology Division, Harvard Institute of Medicine, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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