Document Detail


Degradation of B-Myb by ubiquitin-mediated proteolysis: involvement of the Cdc34-SCF(p45Skp2) pathway.
MedLine Citation:
PMID:  10871850     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
B-Myb, a highly conserved member of the Myb oncoprotein family, is a 110 kDa sequence-specific DNA binding protein expressed in virtually all proliferating cells. B-myb expression reaches its maximum at the G1/S phase boundary and during the S phase of the cell cycle. We have previously shown that B-Myb activity is cell cycle regulated and it is controlled by the antagonistic effects of cyclin D1 and A. Here we show that ectopic expression of cyclin A causes a pronounced reduction of B-Myb protein level. We provide evidence that in addition to triggering B-Myb activity an important effect of cyclin A is to facilitate multiple ubiquitination of B-Myb. The C-terminal domain of B-Myb is of key importance in mediating this effect of cyclin A. Contrary to full-length B-Myb, a C-terminal deletion mutant displays activity irrespective of cyclin A expression, does not undergo ubiquitination, and its half-life is not affected by cyclin A. Ectopic expression of either Cdc34 or the F-box protein p45Skp2, respectively the E2 and E3 components of a ubiquitination pathway that regulates the G1/S transition, accelerates degradation of B-Myb. We show that B-Myb physically and functionally interacts with components of the Cdc34-SCFp45Skp2 ubiquitin pathway and propose that B-Myb degradation may be required for controlling the correct alternation of events during progression through the cell division cycle. Oncogene (2000).
Authors:
S Charrasse; I Carena; V Brondani; K H Klempnauer; S Ferrari
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncogene     Volume:  19     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-07-12     Completed Date:  2000-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2986-95     Citation Subset:  IM    
Affiliation:
Department of Oncology, Novartis Pharma AG, Klybeckstrasse 141, 4057 Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle Proteins / metabolism*
Cell Line
Cyclin A / metabolism
Cysteine Endopeptidases / metabolism
DNA-Binding Proteins / metabolism*
Humans
Hydrolysis
Ligases / metabolism*
Multienzyme Complexes / metabolism
Proteasome Endopeptidase Complex
Protein Binding
S-Phase Kinase-Associated Proteins
Trans-Activators / metabolism*
Ubiquitin-Protein Ligase Complexes*
Ubiquitin-Protein Ligases
Ubiquitins / metabolism*
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin A; 0/DNA-Binding Proteins; 0/MYBL2 protein, human; 0/Multienzyme Complexes; 0/S-Phase Kinase-Associated Proteins; 0/Trans-Activators; 0/Ubiquitins; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.25.1/Proteasome Endopeptidase Complex; EC 6.-/Ligases; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/anaphase-promoting complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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