Document Detail

The hematopoietic transcription factor AML1 (RUNX1) is negatively regulated by the cell cycle protein cyclin D3.
MedLine Citation:
PMID:  16287839     Owner:  NLM     Status:  MEDLINE    
The family of cyclin D proteins plays a crucial role in the early events of the mammalian cell cycle. Recent studies have revealed the involvement of AML1 transactivation activity in promoting cell cycle progression through the induction of cyclin D proteins. This information in combination with our previous observation that a region in AML1 between amino acids 213 and 289 is important for its function led us to investigate prospective proteins associating with this region. We identified cyclin D3 by a yeast two-hybrid screen and detected AML1 interaction with the cyclin D family by both in vitro pull-down and in vivo coimmunoprecipitation assays. Furthermore, we demonstrate that cyclin D3 negatively regulates the transactivation activity of AML1 in a dose-dependent manner by competing with CBFbeta for AML1 association, leading to a decreased binding affinity of AML1 for its target DNA sequence. AML1 and its fusion protein AML1-ETO have been shown to shorten and prolong the mammalian cell cycle, respectively. In addition, AML1 promotes myeloid cell differentiation. Thus, our observations suggest that the direct association of cyclin D3 with AML1 functions as a putative feedback mechanism to regulate cell cycle progression and differentiation.
Luke F Peterson; Anita Boyapati; Velvizhi Ranganathan; Atsushi Iwama; Daniel G Tenen; Schickwann Tsai; Dong-Er Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  25     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-18     Completed Date:  2005-12-28     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10205-19     Citation Subset:  IM    
Dept. of Molecular Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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MeSH Terms
CCAAT-Enhancer-Binding Protein-alpha / genetics,  metabolism
Cell Line
Cercopithecus aethiops
Core Binding Factor Alpha 2 Subunit / genetics,  metabolism*
Cyclin D3
Cyclins / genetics,  metabolism*
DNA / metabolism
Gene Expression Regulation*
Histone Deacetylases / metabolism
Protein Binding
Transcriptional Activation / genetics
Grant Support
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-alpha; 0/CCND3 protein, human; 0/Core Binding Factor Alpha 2 Subunit; 0/Cyclin D3; 0/Cyclins; 9007-49-2/DNA; EC Deacetylases

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