Linked Life Data

17215484

Source:http://linkedlifedata.com/resource/pubmed/id/17215484

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-28
pubmed:abstractText
c-Myc is a transcription modulator proto-oncogene. When overexpressed, it becomes an important contributor to the multi-hit process of malignant transformation. In two earlier papers in this journal (see refs. 19 , 20) we reported that retro-inverso peptidomimetic molecules inspired by the Helix-1 of c-Myc motif could be sequence-specific antiproliferative agents active in the low micromolar range. We also found that our peptides were not opening the four-alpha-helix Myc:Max bundle. Their antiproliferative activity in cancer cell lines needs the presence of side chains projecting outside of the bundle in the corresponding native H1 motif. This observation suggested interference with an external partner. In this study we investigated the INI1:Myc interaction. INI1 is a subunit of the SWI/SNF complex (component of the enhanceosome surrounding Myc:Max heterodimer). The INI1:Myc interaction was confirmed via pull down, ELISA, and fluorescence anisotropy assays. According to the length of INI1 fragments used, we calculated Kds ranging between 1.3x10(-6) and 4.8x10(-7) M. The three different techniques applied showed that the INI1:Myc interaction was also the target of our retro-inverso peptidomimetic molecules, which seem to bind specifically at INI1. A Myc binding, 21aa INI1 fragment (minimum interacting sequence), could inspire the synthesis of a new class of more selective c-Myc inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1256-63
pubmed:meshHeading
pubmed-meshheading:17215484-Amino Acid Sequence, pubmed-meshheading:17215484-Anisotropy, pubmed-meshheading:17215484-Antineoplastic Agents, pubmed-meshheading:17215484-Biochemistry, pubmed-meshheading:17215484-Chromosomal Proteins, Non-Histone, pubmed-meshheading:17215484-DNA-Binding Proteins, pubmed-meshheading:17215484-Humans, pubmed-meshheading:17215484-Kinetics, pubmed-meshheading:17215484-Microscopy, Fluorescence, pubmed-meshheading:17215484-Molecular Sequence Data, pubmed-meshheading:17215484-Neoplasms, pubmed-meshheading:17215484-Peptides, pubmed-meshheading:17215484-Protein Conformation, pubmed-meshheading:17215484-Protein Interaction Mapping, pubmed-meshheading:17215484-Protein Structure, Secondary, pubmed-meshheading:17215484-Proto-Oncogene Proteins c-myc, pubmed-meshheading:17215484-Transcription Factors
pubmed:year
2007
pubmed:articleTitle
Inhibition of a protein-protein interaction between INI1 and c-Myc by small peptidomimetic molecules inspired by Helix-1 of c-Myc: identification of a new target of potential antineoplastic interest.
pubmed:affiliation
Department of Oncology, Biology and Genetics, University of Genoa, L. go R. Benzi 10, Genoa 16132, Italy. luca.bagnasco@unige.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't