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A thermally targeted peptide inhibitor of symmetrical dimethylation inhibits cancer-cell proliferation.

A thermally targeted peptide inhibitor of symmetrical dimethylation inhibits cancer-cell proliferation.

Authors :
Bidwell GL 3rd
Whittom AA
Thomas E
Lyons D
Hebert MD
Raucher D
Source :
Peptides [Peptides] 2010 May; Vol. 31 (5), pp. 834-41. Date of Electronic Publication: 2010 Feb 16.
Publication Year :
2010

Abstract

Targeting splicing machinery components is an underdeveloped strategy for cancer therapy. Uridine-rich small nuclear ribonucleoproteins (UsnRNPs) are essential spliceosome components that recognize splice sites in newly transcribed RNA. The major spliceosomal snRNPs are comprised of UsnRNA bound by a ring of Sm proteins. The survival of motor neuron (SMN) complex provides specificity for binding of Sm proteins to UsnRNAs. Three of the seven proteins that comprise the Sm core possess post-translationally modified C-terminal symmetric dimethylarginine (sDMA) residues which promote binding of these proteins to SMN. Here we describe a peptide inhibitor of sDMA that is capable of interfering with SMN/SmB interaction. The inhibitory peptide was attached to elastin-like polypeptide, a thermally responsive macromolecular carrier, in order to increase its stability and allow enhancement of its cellular uptake by thermal targeting. The fusion polypeptide inhibited the interaction of SMN/SmB, inhibited proliferation, and induced apoptosis in HeLa cells.<br /> (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1873-5169
Volume :
31
Issue :
5
Database :
MEDLINE
Journal :
Peptides
Publication Type :
Academic Journal
Accession number :
20167239
Full Text :
https://doi.org/10.1016/j.peptides.2010.02.007