Document Detail

c-myb transactivates the human cyclin A1 promoter and induces cyclin A1 gene expression.
MedLine Citation:
PMID:  10590070     Owner:  NLM     Status:  MEDLINE    
Cyclin A1 differs from other cyclins in its highly restricted expression pattern. Besides its expression during spermatogenesis, cyclin A1 is also expressed in hematopoietic progenitor cells and in acute myeloid leukemia. We investigated mechanisms that might contribute to cyclin A1 expression in hematopoietic cells. Comparison of cyclin A1 and cyclin A promoter activity in adherent and myeloid leukemia cell lines showed that the cyclin A1 promoter is preferentially active in myeloid cell lines. This preferential activity was present in a small, 335-bp cyclin A1 promoter fragment that contained several potential c-myb binding sites. Coexpression of a c-myb expression vector with the cyclin A1 promoter constructs significantly increased the reporter activity in adherent CV-1 as well as in myeloid U937 cells. Gel-shift assays demonstrated that c-myb could bind to the cyclin A1 promoter at a binding site located near the transcription start site. Site-directed mutagenesis of this site decreased promoter transactivation by 50% in both KCL22 cells that express high levels of c-myb and in CV-1 cells that were transfected with c-myb. In addition, transfection of primary human embryonic fibroblasts with a c-myb expression vector led to induction of the endogenous cyclin A1 gene. Taken together, c-myb can directly transactivate the promoter of cyclin A1, and c-myb might be involved in the high-level expression of cyclin A1 observed in acute myeloid leukemia. These findings suggest that c-myb induces hematopoiesis-specific mechanisms of cell cycle regulation.
C Müller; R Yang; G Idos; N Tidow; S Diederichs; O M Koch; W Verbeek; T P Bender; H P Koeffler
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Blood     Volume:  94     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-10     Completed Date:  2000-01-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4255-62     Citation Subset:  AIM; IM    
Division of Hematology/Oncology, Cedars-Sinai Research Institute/UCLA School of Medicine, Los Angeles, CA, USA.
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MeSH Terms
Base Sequence
Cloning, Molecular
Cyclin A / genetics*
Cyclin A1
Gene Expression Regulation, Neoplastic*
Genes, myb*
Hela Cells
Molecular Sequence Data
Promoter Regions, Genetic*
Grant Support
Reg. No./Substance:
0/CCNA1 protein, human; 0/Cyclin A; 0/Cyclin A1

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