Linked Life Data

17077080

Source:http://linkedlifedata.com/resource/pubmed/id/17077080

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2006-12-25
pubmed:abstractText
Post-translational modifications, such as phosphorylation, acetylation, ubiquitination, and SUMOylation, play an important role in regulation of the stability and the transcriptional activity of c-Myb. Conjugation of small ubiquitin-like modifier type 1 (SUMO-1) to lysines in the negative regulatory domain strongly suppresses its transcriptional activity. Here we report conjugation of two other members of the SUMO protein family, SUMO-2 and SUMO-3, and provide evidence that this post-translational modification negatively affects transcriptional activity of c-Myb. Conjugation of SUMO-2/3 proteins is strongly enhanced by several different cellular stresses and occurs primarily on two lysines, Lys(523) and Lys(499). These lysines are in the negative regulatory domain of c-Myb and also serve as acceptor sites for SUMO-1. Stress-induced SUMO-2/3 conjugation is very rapid and independent of activation of stress-activated protein kinases of the SAPK and JNK families. PIAS-3 protein was identified as a new c-Myb-specific SUMO-E3 ligase that both catalyzes conjugation of SUMO-2/3 proteins to c-Myb and exerts a negative effect on c-Myb-induced reporter gene activation. Interestingly, co-expression of a SPRING finger mutant of PIAS-3 significantly suppresses SUMOylation of c-Myb under stress. These results argue that PIAS-3 SUMO-E3 ligase plays a critical role in stress-induced conjugation of SUMO-2/3 to c-Myb. We also detected stress-induced conjugation of SUMO-2/3 to c-Myb in hematopoietic cells at the levels of endogenously expressed proteins. Furthermore, according to the negative role of SUMO conjugation on c-Myb capacity, we have observed rapid stress-induced down-regulation of the targets genes c-myc and bcl-2 of c-Myb. Our findings demonstrate that SUMO-2/3 proteins conjugate to c-Myb and negatively regulate its activity in cells under stress.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40065-75
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17077080-Animals, pubmed-meshheading:17077080-COS Cells, pubmed-meshheading:17077080-Cell Line, Transformed, pubmed-meshheading:17077080-Cell Line, Tumor, pubmed-meshheading:17077080-Cercopithecus aethiops, pubmed-meshheading:17077080-Down-Regulation, pubmed-meshheading:17077080-Leukemia, Erythroblastic, Acute, pubmed-meshheading:17077080-Lysine, pubmed-meshheading:17077080-MAP Kinase Signaling System, pubmed-meshheading:17077080-Mice, pubmed-meshheading:17077080-Mutagenesis, Site-Directed, pubmed-meshheading:17077080-Osmotic Pressure, pubmed-meshheading:17077080-Protein Processing, Post-Translational, pubmed-meshheading:17077080-Proto-Oncogene Proteins c-myb, pubmed-meshheading:17077080-Small Ubiquitin-Related Modifier Proteins, pubmed-meshheading:17077080-Stress, Physiological, pubmed-meshheading:17077080-Trans-Activators, pubmed-meshheading:17077080-Ubiquitins
pubmed:year
2006
pubmed:articleTitle
Stress-induced inactivation of the c-Myb transcription factor through conjugation of SUMO-2/3 proteins.
pubmed:affiliation
Center of Molecular Medicine, Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovakia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't