Linked Life Data

16861907

Source:http://linkedlifedata.com/resource/pubmed/id/16861907

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2006-8-24
pubmed:abstractText
Azurin is a periplasmic 128 amino acid protein in Pseudomonas aeruginosa, termed Paz, which has been shown to enter preferentially and induce apoptosis in cancer cells such as human melanoma or breast cancer. Its effectiveness against brain tumors such as glioblastomas has not been studied. The meningitis-causing bacterium Neisseria meningitidis also harbors an azurin-like protein. Unlike all other known azurins, Neisserial azurin, termed Laz, is surface-exposed and has in its N-terminal region a 39 amino acid epitope called H.8. Upstream of this H.8 moiety is a lipobox that results in the truncation of the protein at the N-terminal cysteine residue with modification by a lipid group. No function of Laz is known. We demonstrate that while Paz is deficient in entering glioblastoma cells and exhibits low cytotoxicity, Laz is much more proficient in entering glioblastoma cells and shows a higher level of cytotoxicity. When the Neisserial H.8 moiety containing the lipobox is fused in frame with Paz either in its N-terminal (H.8-Paz) or in its C-terminal (Paz-H.8), both had high cytotoxicity for glioblastoma cells and a higher level of internalization. When expressed in E. coli, H.8-Paz was much more exposed on the surface than Paz-H.8. The replacement of the Laz N-terminal cysteine residue involved in acylation with an alanine residue abolished the surface display, but had no effect on cytotoxicity or entry in glioblastoma cells, suggesting a role of the H.8 moiety, but not its lipidation, in disrupting the entry barrier in brain tumor cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1633-41
pubmed:meshHeading
pubmed-meshheading:16861907-Azurin, pubmed-meshheading:16861907-Bacterial Outer Membrane Proteins, pubmed-meshheading:16861907-Brain Neoplasms, pubmed-meshheading:16861907-Cell Death, pubmed-meshheading:16861907-Cloning, Molecular, pubmed-meshheading:16861907-Epitopes, pubmed-meshheading:16861907-Escherichia coli, pubmed-meshheading:16861907-Gene Expression, pubmed-meshheading:16861907-Glioblastoma, pubmed-meshheading:16861907-Humans, pubmed-meshheading:16861907-Lipids, pubmed-meshheading:16861907-Membrane Proteins, pubmed-meshheading:16861907-Mutant Proteins, pubmed-meshheading:16861907-Neisseria meningitidis, pubmed-meshheading:16861907-Peptides, pubmed-meshheading:16861907-Periplasmic Proteins, pubmed-meshheading:16861907-Protein Transport, pubmed-meshheading:16861907-Recombinant Fusion Proteins, pubmed-meshheading:16861907-Tumor Cells, Cultured
pubmed:year
2006
pubmed:articleTitle
Disrupting the entry barrier and attacking brain tumors: the role of the Neisseria H.8 epitope and the Laz protein.
pubmed:affiliation
Department of Microbiology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't