Document Detail

Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function.
MedLine Citation:
PMID:  11264176     Owner:  NLM     Status:  MEDLINE    
Cyclin A1 is tissue-specifically expressed during spermatogenesis, but it is also highly expressed in acute myeloid leukemia (AML). Its pathogenetic role in AML and in the cell cycle of leukemic blasts is unknown. B-myb is essential for G1/S transition and has been shown to be phosphorylated by the cyclin A2/cdk2 complex. Here it is demonstrated that cyclin A1 interacts with the C-terminal portion of B-myb as shown by glutathione S-transferase (GST) precipitation. This interaction is confined to cyclin A1 because binding could not be detected between cyclin A2 and B-myb. Also, cdk2 was not pulled down by GST-B-myb from U937 lysates. In addition, co-immunoprecipitation of cyclin A1 and B-myb in leukemic cells evidenced protein interaction in vivo. Baculovirus-expressed cyclin A1/cdk2 complexes were able to phosphorylate human as well as murine B-myb in vitro. Tryptic phosphopeptide mapping revealed that cyclin A1/cdk2 complexes phosphorylated the C-terminal part of B-myb at several sites including threonine 447, 490, and 497 and serine 581. These phosphorylation sites have been demonstrated to be important for the enhancement of B-myb transcriptional activity. Further studies showed that cyclin A1 cooperated with B-myb to transactivate myb binding site containing promoters including the promoter of the human cyclin A1 gene. Taken together, the data suggest that cyclin A1 is a tissue-specific regulator of B-myb function and activates B-myb in leukemic blasts. (Blood. 2001;97:2091-2097)
C Müller-Tidow; W Wang; G E Idos; S Diederichs; R Yang; C Readhead; W E Berdel; H Serve; M Saville; R Watson; H P Koeffler
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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:  97     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-26     Completed Date:  2001-04-26     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2091-7     Citation Subset:  AIM; IM    
Department of Medicine, Hematology, and Oncology, University of Münster, Germany.
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MeSH Terms
CDC2-CDC28 Kinases*
Cell Cycle Proteins*
Cyclin A / physiology*
Cyclin A1
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases / physiology*
DNA-Binding Proteins / physiology*
Gene Expression Regulation / physiology*
Hematopoietic Stem Cells / metabolism*
Macromolecular Substances
Neoplastic Stem Cells / metabolism*
Organ Specificity
Peptide Mapping
Phosphoserine / chemistry*
Phosphothreonine / chemistry*
Promoter Regions, Genetic
Protein Processing, Post-Translational*
Protein-Serine-Threonine Kinases / physiology*
Trans-Activators / physiology*
Transcription, Genetic / physiology*
U937 Cells / metabolism
Reg. No./Substance:
0/CCNA1 protein, human; 0/Ccna1 protein, mouse; 0/Cell Cycle Proteins; 0/Cyclin A; 0/Cyclin A1; 0/DNA-Binding Proteins; 0/MYBL2 protein, human; 0/Macromolecular Substances; 0/Mybl2 protein, mouse; 0/Trans-Activators; 1114-81-4/Phosphothreonine; 17885-08-4/Phosphoserine; EC Kinases; EC Kinases; EC protein, human; EC protein, mouse; EC Kinase 2; EC Kinases
Comment In:
Blood. 2001 Apr 1;97(7):1905C-1905   [PMID:  11264149 ]

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