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Protein Degradation. Vol. 1Ц4. Edited by R.John Mayer AaronJ

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Protein Degradation
Vol. 1–4. Edited by
R. John Mayer,
Aaron J. Ciechanover and Martin
Rechsteiner. WileyVCH, Weinheim
2007. 1203 pp.,
E 495.00.—ISBN
Several times in the past, discoveries
about different aspects of protein synthesis have earned a Nobel Prize. In
contrast to that, many questions about
the breakdown of cell proteins remained
unanswered for a long time. The discovery of lysosomes by Christian De Duve
in 1955 led many scientists to suspect
that these organelles were responsible
for protein degradation. However, it was
not until the end of the 1970s that
Herschko, Ciechanover, and Rose
began their researches that eventually
revealed the dominant role of the ubiquitin–proteasome system in the breakdown of cell proteins, which culminated
in the award of a Nobel Prize to the
three scientists in 2004. The substrates
that are affected by the ubiquitindependent proteolysis include cyclins,
receptor tyrosine kinases, transcription
factors, p53, viral proteins, and many
others. Thus, the ubiquitin-proteasome
system is an important regulator of
various processes, such as signal transduction, cell division, and cell differentiation. It is also involved in pathologically malignant, neurodegenerative,
immunological, and inflammatory diseases. Much knowledge has now been
accumulated in the area of proteasomedependent protein degradation, and the
time was ripe for at least a part of this to
be collected together in book form. In
this four-volume work Protein Degradation, the editors bring together knowledge about the many different facets of
the proteasomes and the ubiquitins,
from the fundamentals to the cellbiological, clinical, and therapeutic
Volume 1 begins with a short historical survey about ubiquitin, then
explains the biological principles of the
ubiquitination of proteins, with the help
of appropriate examples. Here the
reader learns about some basic details,
and gains interesting insights into the
discovery process. The structure and
function of the so-called RING finger
proteins (ubiquitin–protein E3-ligases,
such as Mdm2 and Mdmx) is discussed
in connection with the regulation of the
tumor-suppressant protein p53. That is
followed by a chapter on the structural
biology of the ubiquitin–protein ligases,
including a discussion of some aspects of
substrate recognition and specificity.
Next there are two chapters on the 26S
proteasome, covering its structure, biochemical properties, biogenesis, and the
molecular mechanism of its function.
The volume ends with a chapter on the
signalosome and its importance for the
ubiquitin system.
Volume 2 begins with a chapter on
molecular chaperones (the Hsp70 and
Hsp90 family) and their function in the
breakdown of wrongly folded proteins.
The topics that are covered briefly here
include endogenous proteasome activators, proteasome-interacting proteins,
and especially the structure, mechanism of action, and development of
small-molecule proteasome inhibitors.
Examples of such inhibitors are peptide aldehydes, epoxyketones, lactacystine, vinylsulfones, and peptide boronates.
Volume 3 is devoted to topics concerned with cell biology. Here several
chapters deserve a special mention, first
the one on the ubiquitin system and its
relationship to the functions of peroxisomes and lysosomes, and to muscle
development. The regulation of cell
hypoxie (through the breakdown of
the HIF-1a factor) and of the p97
protein (ATPase) are discussed in
detail (the latter in two consecutive
chapters). The volume ends with a
( 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
chapter on the role of de-ubiquitinated
enzymes in cell proliferation and in
Volume 4 is the one that I personally
liked best, as it gives the reader a very
clear description of medical aspects of
the ubiquitin–proteasome system. The
chapters describe how ubiquitination
controls the cell cycle, the repair of
DNA, angiogenesis, the activity of
receptor tyrosine kinases, and NF-kB
signal cascades, and modulates the activity of p53. Various possibilities for
targeting the ubiquitin–proteasome
system in connection with the development of new therapies for malignant
diseases are discussed, as well as the
mechanism and scope of application of
bortezomib (which inhibits the breakdown of p53 and IkB as one of its
effects). The chapters discuss the importance of ubiquitin-mediated viral infections (the Ebstein–Barr virus) and oncogenesis (in cervical cancer) and the
involvement of ubiquitin in the pathogenesis of neurodegenerative diseases,
and describe some important examples.
All four volumes are well written
and have a wealth of color illustrations.
The literature is covered up to the year
of publication of the individual volumes.
The repetitions of some aspects (as
commonly happens in multi-author
works) were probably unavoidable. I
would have liked abstracts of all the
contributions, in a consistent form, to be
included. Not all the abbreviations have
been explained. In some cases the same
topic is treated in different volumes (for
example, signalosome is discussed in
Volumes 1 and 3). Unfortunately, information about some pharmacological
agents (e.g., bortezomib) is difficult to
find and is meager. Bortezomib, an
important agent for the treatment of
multiple myeloma and other cancers, is
not even mentioned in the index, despite
the fact that over 500 reviews on it have
been published.
Despite these minor shortcomings,
this work is important and can be
recommended, as it provides insights
into, and brings order to, a rapidly
developing and highly topical area of
life sciences. I hope that an updated edition will eventually be published, and that it will contain a
more detailed discussion of design
Angew. Chem. Int. Ed. 2008, 47, 5880 – 5881
and clinical aspects of proteasome inhibitors.
Athanassios Giannis
Institut f1r Organische Chemie
Universit4t Leipzig (Germany)
DOI: 10.1002/anie.200885586
Hydrogen Energy
Challenges and
Prospects. By
D. A. J. Rand and
R. M. Dell. Royal
Society of Chemistry, Cambridge
2007. 300 pp.,
£ 45.00.—ISBN
The total world energy consumption
increased drastically from 253 EJ/a in
1973 to 463 EJ/a in 2004 (1 EJ = 1018 J),
a rise of 83 % in 31 years, and it is
projected by the International Energy
Agency (IEA) to reach 691 EJ/a by
2030. In the light of these figures,
together with the need to reduce CO2
emissions and their effects on climate
change, and the mid-term decline of
fossil fuel reserves of coal, oil, and
natural gas, the future security of
energy supplies has become a major
issue that is being discussed throughout
the world. Much of the content in this
book is centered around the analysis of
the current situation and the possible
solutions. One option is an energy
system with hydrogen as a secondary
energy carrier (the “hydrogen economy”). How does hydrogen fit into the
evolving energy scene of emerging technologies that include renewables like
wind, solar energy, and hydro-power?
The book sets out to explain the
concept of hydrogen as an energy
Angew. Chem. Int. Ed. 2008, 47, 5880 – 5881
vector, to identify the barriers to its
implementation, and to explore prospects for success. The vision of a hydrogen economy is evaluated critically by
the authors, who are both senior
research chemists and have spent their
entire professional careers in the energy
field. Emphasis has been placed on
technical matters rather than addressing
sociological, political, legal, or fiscal
Chapter 1 deals with general aspects
of the security of energy supply, climate
change, atmospheric pollution, electricity generation, and hydrogen as a fuel,
and takes a critical view of the complexity of a future hydrogen economy.
Chapter 2 considers the different
routes for generating hydrogen from
fossil fuels and biomass, and looks in
detail at reforming and process technologies for natural gas, including gas
separation processes, steam reforming
of methane, solar-thermal reforming,
partial oxidation of hydrocarbons, and
other processes such as autothermal,
sorbent-enhanced, and plasma reforming. Gas separation using membrane
reactors, gasification technology, and
combined-cycle processes such as
CCGT and IGCC are also discussed.
Biomass, dry or wet, as a carbon-based
solid fuel that is a renewable form of
energy, is also included in this chapter.
Chapter 3 deals with questions of
scale in carbon sequestration, capture of
carbon dioxide by post-combustion,
oxy-fuel, chemical looping, and precombustion technology. Geological
aspects, mineral carbonation, ocean
storage options, and re-use of carbon
dioxide are discussed. Chapter 4 looks at
technologies for generating hydrogen
from water, including electrolysis,
decomposition of water using solar
energy, solar-thermal processes, photoelectrochemical and photo-biochemical
cells, and thermochemical routes based
on sulfur–iodine, sulfur–ammonia, and
metal oxide cycles. In Chapter 5, the
authors discuss strategies for the distribution and storage of gaseous and liquid
hydrogen, including metal hydrides and
other hydrogen-bearing chemicals, as
well as complex and nano-structured
Chapter 6 is devoted to fuel cells as a
key technology for a future hydrogen
economy, particularly for electricity
generation and electric vehicle propulsion. After a short historical review, the
fundamentals of fuel cell operation and
the different types of cells are explained.
Thermodynamic aspects and differences
between the efficiencies of large- and
small-scale fuel cell power generation
units are briefly discussed. Chapter 7
gives an overview of recent developments in hydrogen-fueled transportation, hybrid electric cars, aircraft, submarine, and other fuel-cell-driven vehicles. “Hydrogen Highways” that are
projected in the USA, Canada, and
Europe are described, with a neat calculation of efficiencies and fuel consumption. The final chapter draws
together the main conclusions reached,
with an attempt to predict the prospects
for hydrogen in the world energy scene
over the next 40–50 years.
The book is a valuable source of upto-date information, with a wealth of
data thoroughly collected and referenced at the end of each chapter. It
contains a list of abbreviations, symbols,
and units, a glossary of terms, and
conversion factors for units and useful
quantities. It is well illustrated with
photos, schematic drawings, and presentations of data in graphs or tables.
Complex mathematical formulas are
avoided, which makes the book easy to
read and suitable for a wide readership
with the common background of natural
Gerhard Kreysa, Klaus J"ttner
Frankfurt am Main (Germany)
( 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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degradation, mayer, protein, edited, 1ц4, vol, john, aaron
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