Document Detail

Myb-dependent regulation of thrombospondin 2 expression. Role of mRNA stability.
MedLine Citation:
PMID:  9694906     Owner:  NLM     Status:  MEDLINE    
The nuclear transcription factor c-Myb, which is highly expressed in hematopoietic cells, has been shown to be functional in NIH 3T3 cells: cells that do not possess detectable levels of c-Myb. To identify endogenous target genes of c-Myb in fibroblasts, RNA isolated from NIH 3T3 cells stably transfected with a full-length or a dominant negative c-myb construct (GREMyb and GREMEn, respectively) was subjected to differential display analysis. 5'-Rapid amplification of cDNA ends of a selected band, sequencing, and a nucleotide homology search led to the identification of thrombospondin 2 (TSP 2) as the gene product repressed in GREMyb and induced in GREMEn cells. The pattern of TSP 2 expression during the cell cycle was consistent with c-myb-dependent regulation. The possibility that the identified transcript was TSP 1, a homologous product known to be repressed by v-Src, c-Jun, and v-Myc, was ruled out by using a TSP 2-specific DNA probe and by showing a distinct pattern of regulation of TSP 1 and TSP 2 expression. Nuclear run-on and TSP 2 promoter-reporter (chloramphenicol acetyltransferase) assays showed similar transcriptional levels in GREMyb and NIH 3T3 cells. However, mRNA stability studies showed a much shorter TSP 2 mRNA half-life in GREMyb compared with wild type NIH 3T3 cells, suggesting that c-myb affects TSP 2 expression via a post-transcriptional mechanism. The implications of a protooncogene-mediated suppression of TSP expression are discussed.
K Bein; J A Ware; M Simons
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  273     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-09-14     Completed Date:  1998-09-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  21423-9     Citation Subset:  IM    
Angiogenesis Research Center, Cardiovascular Division, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
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MeSH Terms
3T3 Cells
Base Sequence
Cloning, Molecular
DNA Primers
Gene Expression Regulation*
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-myb
RNA, Messenger / genetics
Thrombospondins / genetics*
Trans-Activators / metabolism*
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/DNA Primers; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myb; 0/RNA, Messenger; 0/Thrombospondins; 0/Trans-Activators; 0/thrombospondin 2

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