Linked Life Data

11073948

Source:http://linkedlifedata.com/resource/pubmed/id/11073948

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-5-23
pubmed:abstractText
The c-myb proto-oncogene product (c-Myb) is a sequence-specific DNA-binding protein that functions as a transcriptional activator. The transcriptional coactivator CREB-binding protein (CBP) binds via its KIX domain to the activation domain of c-Myb and mediates c-Myb-dependent transcriptional activation. CBP possesses intrinsic histone acetyltransferase activity, and can acetylate not only histones but also certain transcriptional factors such as GATA1 and p53. Here we demonstrate that the C/H2 domain of CBP, which is critical for the acetyltransferase activity, also directly interacts with the negative regulatory domain (NRD) of c-Myb. Consistent with this observation, CBP acetylated c-Myb in vitro at Lys(438) and Lys(441) within the NRD. In addition, CBP acetylated c-Myb in vivo not only at the sites found in this study but also at the p300-induced acetylation sites reported recently. Replacement of lysine by arginine at all of these sites dramatically decreased the trans-activating capacity of c-Myb. The results of transcriptional activation assays with c-Myb acetylation site mutants suggested that acetylation of c-Myb at each of these five sites synergistically enhances c-Myb activity. Mutations of these acetylation sites reduced the strength of the interaction between c-Myb and CBP. Thus, acetylation of c-Myb by CBP increases the trans-activating capacity of c-Myb by enhancing its association with CBP. These results demonstrate a novel molecular mechanism of regulation of c-Myb activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3674-82
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Increased affinity of c-Myb for CREB-binding protein (CBP) after CBP-induced acetylation.
pubmed:affiliation
Laborartory of Molecular Genetics, RIKEN Tsukuba Institute and the CREST (Core Research for Evolutional Science and Technology) Research Project of JST (Japan Science and Technology Corporation), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't