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Identification of variable region differences in Neisseria meningitidis class 3 protein sequences among five group B serotypes (1992)

Zapata, Gerardo A. ; Vann, Willie F. ; Rubinstein, Yaffa ; [et al.]

Oxford, UK : Blackwell Publishing Ltd

Molecular microbiology 6 (1992), S. 0

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ISSN: 1365-2958

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Biology , Medicine

Notes: Strains of Neisseria meningitidis express one of two porin proteins. These porins have been identified as the class 2 and class 3 proteins, and express serotype-specific epitopes. The gene for the class 3 protein was amplified by the polymerase chain reaction from the DNA of a serotype 4 strain as a 1025bp fragment. The nucleotide sequence of this gene was determined and compared with two recently published sequences. On the basis of this comparison we have identified two major variable regions in the translated protein sequence, VR1 and VR2, that may be associated with serotype specificity. Three other variable regions were also identified. The sequences in the VR1 and VR2 regions from five additional group B N. meningitidis strains of serotypes 1, 4, 8,12, and 15, all expressing class 3 proteins, were determined. The VR1 and VR2 regions were variable and were flanked by highly conserved regions among eight different class 3 sequences. These two variable regions of 15 and 9 amino acids are predicted to be in surface-exposed loops.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1111/j.1365-2958.1992.tb01784.x

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Inhibition of NF-κB Activity Enhances TRAIL Mediated Apoptosis in Breast Cancer Cell Lines (2000)

Keane, Maccon M. ; Rubinstein, Yaffa ; Cuello, Mauricio ; [et al.]

Springer

Breast cancer research and treatment 64 (2000), S. 211-219

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ISSN: 1573-7217

Keywords: apoptosis ; breast cancer ; caspases ; NF-κB ; TRAIL

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract Most breast cancer cell lines are resistant to TNF-related apoptosis inducing ligand (TRAIL) induced apoptosis. In sensitive breast cancer cell lines TRAIL rapidly induces the cleavage and activation of caspases leading to the subsequent cleavage of downstream caspase substrates. In contrast, there is no caspase activation in the resistant cell lines. The transcription factor NF-κB can inhibit apoptosis induced by a variety of stimuli including activation of death receptors. We investigated whether NF-κB contributes to the resistance of breast cancer cells to TRAIL induced apoptosis. All of the resistant breast cancer cell lines expressed NF-κB and had detectable NF-κB activity in nuclear extracts prior to treatment with TRAIL. Upon TRAIL treatment, a significant increase in NF-κB activity was seen in most of the cell lines. To directly test if NF-κB activity contributes to the resistance of these cell lines to TRAIL, we transiently transfected the resistant cell lines with an inhibitor of NF-κB (IκBΔN) and measured TRAIL induced apoptosis in control and transfected cells. All of the resistant cell lines tested showed an increase in TRAIL induced apoptosis when transfected with the IκBΔN. These results demonstrate that TRAIL resistant breast cancer cells fail to rapidly activate the apoptotic machinery but they do activate NF-κB. Inhibition of NF-κB activity increases the sensitivity to TRAIL mediated apoptosis in resistant cells. These results suggest that agents which inhibit NF-κB should increase the clinical efficacy of TRAIL in breast cancer cells.