Linked Life Data

17998933

Source:http://linkedlifedata.com/resource/pubmed/id/17998933

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2008-4-24
pubmed:abstractText
Histone methylation is involved in the regulation of gene expression and DNA replication through alteration of chromatin structure. We earlier showed that SMYD3, a histone H3-lysine 4-specific methyltransferase, is frequently upregulated in human colorectal, liver and breast cancer compared to their matched non-cancerous cells, and that its activity is associated with the growth of these tumors. In the present study, we found that human cancer cells express both the full-length and a cleaved form of SMYD3 protein. Amino acid sequence analysis uncovered that the cleaved form lacks the 34 amino acids in the N-terminal region of the full-length protein. Interestingly, the cleaved protein and mutant protein containing substitutions at glycines 15 and 17, two highly conserved amino acids in the N-terminal region, revealed a higher histone methyltransferase (HMTase) activity compared to the full-length protein. Furthermore, the N-terminal region is responsible for the association with heat shock protein 90alpha (HSP90alpha). These data indicate that the N-terminal region plays an important role for the regulation of its methyltransferase activity and suggest that a structural change of the protein through the cleavage of the region or interaction with HSP90alpha may be involved in the modulation. These findings may help for a better understanding of the mechanisms that modulate the HMTase activity of SMYD3, and contribute to the development of novel anticancer drugs targeting SMYD3 methyltransferase activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2686-92
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Enhanced methyltransferase activity of SMYD3 by the cleavage of its N-terminal region in human cancer cells.
pubmed:affiliation
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't