Current Proteomics
ISSN: 1570-1646
Current Proteomics
Volume 7 Number 1, April 2010
Contents
Oncoproteomics of Neuroblastoma: A Blueprint for Future Progress
Pp. 1-14
H.R. Kumar, X. Zhong, R.J. Hickey, L.H. Malkas and
J.A. Sandoval
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10 Years of SELDI: What Have we Learnt?
Pp. 15-25
W.Wei, A. Martin, P.J. Johnson and D.G. Ward
[Abstract] [Purchase
Article]
Advances in the Study of Mammalian Proteome by Tandem Affinity
Purification – Mass Spectrometry Pp. 26-35
V.D. Soleimani and M.A. Rudnicki
[Abstract] [Purchase
Article]
An Update on Prion Biology and Proteomics
Pp. 36-48
A.R. Roostaee, M.H. Roostaee and X. Roucou
[Abstract] [Purchase
Article]
Differential Serum Level of Specific Haptoglobin
Isoforms in Small Cell Lung Cancer Pp. 49-56
A. Shah, H. Singh, V. Sachdev, J. Lee, S. Yotsukura, R.
Salgia and A. Bharti
[Abstract] [Purchase
Article]
Mass Spectrometry in the Elucidation of the Glycoproteome
of Bacterial Pathogens Pp. 57-81
R.L.J. Graham and S. Hess
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Article]
Abstracts
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Oncoproteomics of Neuroblastoma: A Blueprint for Future
Progress
H.R. Kumar, X. Zhong, R.J. Hickey, L.H. Malkas and
J.A. Sandoval
High-risk neuroblastoma (NB) represents a problematic
tumor phenotype associated with a dreary outlook. Modern molecular
achievements over the last decade have seen the increase and
implementation of ‘omics technologies in oncology that
promises to provide for a deeper comprehension of complex
tumor pathways. The emerging concept of analyzing NB-specific
‘omics profiles to better understand and define the
behavior of advanced-stage tumors along with providing direct
and targeted therapy may ultimately translate into improved
outcomes for high-risk NB. Knowledge of NB proteomics has
gradually become available, but the challenge remains to integrate
data obtained from different levels of biological organization.
In this review, we provide an overview of the proteomics-based
techniques that can be used to advance and accelerate the
discovery of novel molecular biomarkers for NB. By citing
specific examples, we discuss how proteomics has contributed
to the early detection of advanced-stage NB and minimal residual
disease. We end by contemplating the emerging technologies
that are likely to have a high impact on the field of NB in
the near future.
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10 Years of SELDI: What Have we Learnt?
W.Wei, A. Martin, P.J. Johnson and D.G. Ward
Surface enhanced laser desorbtion/ionisation time-of-flight
mass spectrometry (SELDI-TOF-MS or SELDI) combines retentate
chromatography and mass spectrometry in a high-throughput
format. Analytes are captured using chromatographic or immunocapture
surfaces, matrix applied, ionised/desorbed with a laser and
mass spectra acquired. SELDI based proteomics detects peptides
and small proteins (<20 kDa) and may be used to study the
concentrations, modifications and interactions of specific
proteins or to discover proteomic changes associated with
any biological condition of interest. Over the last decade
SELDI has been applied to a wide range of biological samples
but most often in the search for blood-borne biomarkers of
human diseases, especially cancers. As with any biomarker
research many pitfalls such as insufficient sample size, insufficient
quality control, overfitting and bias must be carefully avoided
to provide meaningful results. Initially, very promising results
were obtained using SELDI-based ‘proteomic profiling’
to detect cancer. However, nearly 10 years on from these initial
reports, none of the potential biomarkers discovered by this
approach have entered routine clinical practice. It is now
apparent that SELDI analysis of serum predominantly detects
abundant serum proteins and that ‘biomarkers’
detected in SELDI experiments most likely arise from host
responses to the cancer. SELDI therefore stands at a crossroads:
will some of the biomarker work to date withstand further
validation and help in the development of clinical tests,
will advances in the technology allow deeper proteome mining
or will SELDI become obsolete as a biomarker discovery platform?
We review what has been achieved by SELDI both in, and outside,
of the context of biomarker discovery.
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Advances in the Study of Mammalian Proteome by Tandem Affinity
Purification – Mass Spectrometry
V.D. Soleimani and M.A. Rudnicki
Proper cellular functioning is dependent on the timely
association of thousands of proteins in discrete complexes.
A major challenge in the post genomic era is the elucidation
of these diverse protein complexes and networks that govern
mammalian cellular function and cell fate. Identification
of the individual components of these arrangements is vital
to the understanding of their function in biological processes.
Currently, a widely used technique for the identification
of protein complexes is a combinational approach of Tandem
Affinity Purification coupled with Mass Spectrometry (TAP-MS).
This technique was originally developed for the study of the
yeast proteome but has since been adapted for studies of the
mammalian system. This review discusses the applications of
TAP-MS to the mammalian proteome. Our focus includes the technical
improvements made in each step of the TAP-MS pipeline including
vector design, delivery of the TAP construct into cells, expression
of bait proteins, purification strategies and finally the
identification of the protein complexes by mass spectrometry.
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An Update on Prion Biology and Proteomics
A.R. Roostaee, M.H. Roostaee and X. Roucou
Prion diseases, or transmissible spongiform encephalopathies
(TSEs), are fatal neurodegenerative disorders of humans and
animals caused by conformational conversion of a normal host
glycoprotein (PrPc) into
an infectious isoform (PrPsc).
Whereas the mechanism of PrPsc
formation and its infectivity are the subject of intensive
research, the exact physiological function of PrPc
and the mechanism of neurotoxicity are still unknown. Since
prion infections are not limited to a monofunctional event,
the PrPc/PrPsc
conversion, this review will focus on recent insights into
the biology of the prion protein uncovered by proteomic approaches.
Recent neuroproteomic studies on the protein profile modifications
associated with chronic prion infection in cell systems depicted
the co-occurring biochemical abnormalities which are the basis
of the prion-induced neuronal death and comprise targets for
curative drugs. The involvement of other pathways in prion
infectivity opens new insights into understanding of the mechanism
of cellular toxicity at the molecular level. This can provide
further perspectives for identification of novel therapeutic
targets and also allows an integrated paradigm in the prion
conversion/toxicity biology.
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Differential Serum Level of Specific Haptoglobin
Isoforms in Small Cell Lung Cancer
A. Shah, H. Singh, V. Sachdev, J. Lee, S. Yotsukura, R.
Salgia and A. Bharti
Lung cancer is the leading cause of cancer death for
both men and women in the United States, and similar trends
are seen world wide. The lack of early diagnosis is one of
the primary reasons for the high mortality rate. A number
of biomarkers have been evaluated in lung cancer patients,
however, their specificity and early stage diagnostic values
are limited. Using traditional protein chemistry and proteomics
tool we have demonstrated higher serum haptoglobin levels
in small cell lung cancer (SCLC). Similar findings have been
reported for other cancers including ovarian cancer and glioblastoma.
Haptoglobin is an acute phase protein with at least six possible
phenotypes. The six phenotypes, in combination with two post
translational modifications, glycosylation and deamidation,
lead to large numbers of possible haptoglobin isoforms. Recent
studies indicate a possible correlation between specific haptoglobin
glycosylation and particular disease conditions. In our current
study, we have fractionated control and SCLC patient serum
by 2-D gel electrophoresis to identify differentially expressed
haptoglobin isoforms in SCLC serum samples.
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Mass Spectrometry in the Elucidation of the Glycoproteome
of Bacterial Pathogens
R.L.J. Graham and S. Hess
Presently some three hundred post-translational modifications
are known to occur in bacteria in vivo. Many of these
modifications play critical roles in the regulation of proteins
and control key biological processes. One of the most predominant
modifications, N- and O-glycosylations are now known to be
present in bacteria (and archaea) although they were long
believed to be limited to eukaryotes. In a number of human
pathogens these glycans have been found attached to the surfaces
of pilin, flagellin and other surface and secreted proteins
where it has been demonstrated that they play a role in the
virulence of these bacteria. Mass spectrometry characterization
of these glycosylation events has been the enabling key technology
for these findings. This review will look at the use of mass
spectrometry as a key technology for the detection and mapping
of these modifications within microorganisms, with particular
reference to the human pathogens, Campylobacter jejuni
and Mycobacterium tuberculosis. The overall aim of
this review will be to give a basic understanding of the current
‘state-of-the-art’ of the key techniques, principles
and technologies, including bioinformatics tools, involved
in the analysis of the glycosylation modifications.
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