Document Detail


Linking Myb to the cell cycle: cyclin-dependent phosphorylation and regulation of A-Myb activity.
MedLine Citation:
PMID:  9285555     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A-myb, a conserved member of the Myb proto-oncogene family, encodes a sequence-specific DNA binding protein (A-Myb) that binds to and transactivates promoters containing myb-binding sites. Previous work has suggested that the C-terminus of A-Myb functions as a regulatory domain, however, the physiological signals that control the activity of A-Myb have not yet been identified. The presence of potential phosphorylation sites for cyclin-dependent kinases in the C-terminus of A-Myb has prompted us to examine the possibility that the function of A-Myb is controlled by the cell cycle. We here show that the transactivation potential of A-Myb is repressed by the C-terminal domain and that phosphorylation of A-Myb, induced by cyclins A and E, relieves this inhibitory effect. Our work provides the first evidence that the function of A-Myb is regulated by the cell cycle machinery and that the carboxy-terminal domain of A-Myb acts as a cell cycle sensor. In addition, we show that A-myb mRNA expression is also cell cycle regulated and attains maximal levels during the late G1- and early S-phase. Thus, A-Myb appears to be controlled by two different mechanisms resulting in maximal A-Myb activity during the G1/S-transition and the S-phase of the cell cycle.
Authors:
U Ziebold; K H Klempnauer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  15     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1997 Aug 
Date Detail:
Created Date:  1997-09-22     Completed Date:  1997-09-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1011-9     Citation Subset:  IM    
Affiliation:
Hans-Spemann-Laboratory, Max-Planck-Institute for Immunobiology, Freiburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Cell Cycle* / drug effects
Cyclins / physiology*
DNA-Binding Proteins / metabolism,  physiology
Humans
Mice
Phosphorylation
Protein Structure, Tertiary
Proto-Oncogene Proteins / antagonists & inhibitors,  biosynthesis,  metabolism*,  physiology*
Proto-Oncogene Proteins c-myb
Trans-Activators / antagonists & inhibitors,  biosynthesis,  metabolism*,  physiology*
Chemical
Reg. No./Substance:
0/Cyclins; 0/DNA-Binding Proteins; 0/MYBL1 protein, human; 0/Mybl1 protein, mouse; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myb; 0/Trans-Activators

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