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1.
The vault complex 总被引:2,自引:0,他引:2
van Zon A Mossink MH Scheper RJ Sonneveld P Wiemer EA 《Cellular and molecular life sciences : CMLS》2003,60(9):1828-1837
Vaults are large ribonucleoprotein particles found in eukaryotic cells. They are composed of multiple copies of a M
r 100,000 major vault protein and two minor vault proteins of M
r 193,000 and 240,000, as well as small untranslated RNAs of 86–141 bases. The vault components are arranged into a highly characteristic hollow barrel-like structure of 35 × 65 nm in size. Vaults are predominantly localized in the cytoplasm where they may associate with cytoskeletal elements. A small fraction of vaults are found to be associated with the nucleus. As of yet, the precise cellular function of the vault complex is unknown. However, their distinct morphology and intracellular distribution suggest a role in intracellular transport processes. Here we review the current knowledge on the vault complex, its structure, components and possible functions.Received 23 January 2003; received after revision 13 March 2003; accepted 26 March 2003 相似文献
2.
Proliferating cell nuclear antigen: a proteomics view 总被引:3,自引:0,他引:3
Naryzhny SN 《Cellular and molecular life sciences : CMLS》2008,65(23):3789-3808
Proliferating cell nuclear antigen (PCNA), a cell cycle marker protein, is well known as a DNA sliding clamp for DNA polymerase
delta and as an essential component for eukaryotic chromosomal DNA replication and repair. Due to its mobility inside nuclei,
PCNA is dynamically presented in a soluble or chromatin-associated form. The heterogeneity and specific modifications of PCNA
may reflect its multiple functions and the presence of many binding partners in the cell. The recent proteomics approaches
applied to characterizing PCNA interactions revealed multiple PCNA partners with a wide spectrum of activity and unveiled
the possible existence of new PCNA functions. Since more than 100 PCNA-interacting proteins and several PCNA modifications
have already been reported, a proteomics point of view seems exactly suitable to better understand the role of PCNA in cellular
functions.
Received 29 May 2008; received after revision 7 July 2008; accepted 16 July 2008 相似文献
3.
Protein C inhibitor (PCI) is a widely distributed, multifunctional member of the serpin family of protease inhibitors, and
has been implicated in several physiological processes and disease states. Its inhibitory activity and specificity are regulated
by binding to cofactors such as heparin, thrombomodulin and phospholipids, and it also appears to have non-inhibitory functions
related to hormone and lipid binding. Just how the highly conserved serpin architecture can support the multiple diverse functions
of PCI is a riddle best addressed by protein crystallography. Over the last few years we have solved the structure of PCI
in its native, cleaved and protein-complexed states. They reveal a conserved serpin fold and general mechanism of protease
inhibition, but with some unique features relating to inhibitory specificity/promiscuity, cofactor binding and hydrophobic
ligand transport.
Received 1 July 2008; received after revision 16 August 2008; accepted 22 August 2008 相似文献
4.
Reticulons (RTNs) are membrane-spanning proteins sharing a typical domain named reticulon homology domain (RHD). RTN genes
have been identified in all eukaryotic organisms examined so far, and the corresponding proteins have been found predominantly
associated to the endoplasmic reticulum membranes. In animal and yeast, in which knowledge of the protein family is more advanced,
RTNs are involved in numerous cellular processes such as apoptosis, cell division and intracellular trafficking. Up to now,
a little attention has been paid to their plant counterparts, i.e., RTNLBs. In this review, we summarize the data available for RTNLB proteins and, using the data obtained with animal and
yeast models, several functions for RTNLBs in plant cells are proposed and discussed.
Received 01 July 2008; received after revision 08 September 2008; accepted 30 September 2008 相似文献
5.
A dynamic view of peptides and proteins in membranes 总被引:1,自引:0,他引:1
Bechinger B 《Cellular and molecular life sciences : CMLS》2008,65(19):3028-3039
Biological membranes are highly dynamic supramolecular arrangements of lipids and proteins, which fulfill key cellular functions.
Relatively few high-resolution membrane protein structures are known to date, although during recent years the structural
databases have expanded at an accelerated pace. In some instances the structures of reaction intermediates provide a stroboscopic
view on the conformational changes involved in protein function. Other biophysical approaches add dynamic aspects and allow
one to investigate the interactions with the lipid bilayers. Membrane-active peptides fulfill many important functions in
nature as they act as antimicrobials, channels, transporters or hormones, and their studies have much increased our understanding
of polypeptide-membrane interactions. Interestingly several proteins have been identified that interact with the membrane
as loose arrays of domains. Such conformations easily escape classical high-resolution structural analysis and the lessons
learned from peptides may therefore be instructive for our understanding of the functioning of such membrane proteins.
Received 11 March 2008; received after revision 2 May 2008; accepted 5 May 2008 相似文献
6.
7.
Moorwood C 《Cellular and molecular life sciences : CMLS》2008,65(19):2957-2963
Syncoilin is a member of the intermediate filament protein family, highly expressed in skeletal and cardiac muscle. Syncoilin
binds α-dystrobrevin, a component of the dystrophin associated protein complex (DAPC) located at the muscle cell membrane,
and desmin, a muscle-specific intermediate filament protein, thus providing a link between the DAPC and the muscle intermediate
filament network. This link may be important for muscle integrity and force transduction during contraction, a theory that
is supported by the reduced force-generating capacity of muscles from syncoilin-null mice. Additionally, syncoilin is found
at increased levels in the regenerating muscle fibres of patients with muscular dystrophies and mouse models of muscle disease.
Therefore, syncoilin may be important for muscle regeneration in response to injury. The aims of this article are to review
current knowledge about syncoilin and to discuss its possible functions in skeletal muscle.
Received 21 May 2008; received after revision 10 July 2008; accepted 18 July 2008 相似文献
8.
Wang Y Guan X Fok KL Li S Zhang X Miao S Zong S Koide SS Chan HC Wang L 《Cellular and molecular life sciences : CMLS》2008,65(23):3822-3829
Rhomboid family members are widely conserved and found in all three kingdoms of life. They are serine proteases and serve
important regulatory functions. In the present study, a novel gene highly expressed in the testis, RHBDD1, is shown to be
a new member of the Rhomboid family, participating in the cleavage of BIK, a proapoptotic member of the Bcl-2 family. The
RHBDD1-involved proteolytic modification is upstream of the BIK protein degradation pathway. Mutagenesis studies show that
the amino acid residues glycine142 and serine144 of RHBDD1 are crucial for its activity in cleaving BIK at a site located
in the transmembrane region. Overexpression or knock-down of RHBDD1 in HEK 293T cells can reduce or enhance BIK-mediated apoptosis,
respectively. The present findings suggest that, by acting as a serine protease, RHBDD1 modulates BIK-mediated apoptotic activity.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 31 July 2008; received after revision 16 September 2008; accepted 19 September 2008 相似文献
9.
The cell-cell adhesion molecule E-cadherin 总被引:11,自引:0,他引:11
10.
Inhibiting the production of amyloid-β by antagonising γ-secretase activity is currently being pursued as a therapeutic strategy
for Alzheimer’s disease (AD). However, early pre-clinical studies have demonstrated that disruption of presenilin-dependent
γ-secretase alters many presenilin-dependent processes, leading to early lethality in several AD model organisms. Subsequently,
transgenic animal studies have highlighted several gross developmental side effects arising from presenilin deficiency. Partial
knockdown or tissue-specific knockout of presenilins has identified the skin, vascular and immune systems as very sensitive
to loss of presenilin functions. A more appreciative understanding of presenilin biology is therefore demanded if γ-secretase
is to be pursued as a therapeutic target. Herein we review the current understanding of γ-secretase complexes; their regulation,
abundance of interacting partners and diversity of substrates. We also discuss regulation of the γ-secretase complexes, with
an emphasis on the functional role of presenilins in cell biology.
Received 25 July 2008; received after revision 24 November 2008; accepted 10 December 2008 相似文献
11.
AMP-activated protein kinase in skeletal muscle: From structure and localization to its role as a master regulator of cellular metabolism 总被引:1,自引:0,他引:1
Witczak CA Sharoff CG Goodyear LJ 《Cellular and molecular life sciences : CMLS》2008,65(23):3737-3755
The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator
of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this
review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include
the following: (1) the structural components of the three AMPK subunits (i.e. AMPKα, β, and γ), and their differential localization
in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known
upstream kinases, LKB1, Ca2+/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-β-activated kinase 1 (TAK1); (3) the pharmacological
agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate
AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle.
Received 04 May 2008; received after revision 14 June 2008; accepted 14 July 2008 相似文献
12.
Functions and pathologies of BiP and its interaction partners 总被引:1,自引:1,他引:0
J. Dudek J. Benedix S. Cappel M. Greiner C. Jalal L. Müller R. Zimmermann 《Cellular and molecular life sciences : CMLS》2009,66(9):1556-1569
The endoplasmic reticulum (ER) is involved in a variety of essential and interconnected processes in human cells, including
protein biogenesis, signal transduction, and calcium homeostasis. The central player in all these processes is the ER-lumenal
polypeptide chain binding protein BiP that acts as a molecular chaperone. BiP belongs to the heat shock protein 70 (Hsp70)
family and crucially depends on a number of interaction partners, including co-chaperones, nucleotide exchange factors, and
signaling molecules. In the course of the last five years, several diseases have been linked to BiP and its interaction partners,
such as a group of infectious diseases that are caused by Shigella toxin producing E. coli. Furthermore, the inherited diseases Marinesco-Sj?gren syndrome, autosomal dominant polycystic liver disease, Wolcott-Rallison
syndrome, and several cancer types can be considered BiP-related diseases. This review summarizes the physiological and pathophysiological
characteristics of BiP and its interaction partners.
Received 20 November 2008; received after revision 09 December 2008; accepted 12 December 2008 相似文献
13.
14.
C. Akgul 《Cellular and molecular life sciences : CMLS》2009,66(8):1326-1336
Resistance to apoptosis is a common challenge in human malignancies contributing to both progress of cancer and resistance
to conventional therapeutics. Abnormalities in a variety of cell intrinsic and extrinsic molecular mechanisms cooperatively
promote tumor formation. Therapeutic approaches that specifically target components of these molecular mechanisms are getting
widespread attention. Mcl-1 is a highly expressed pro-survival protein in human malignancies and its cellular expression is
tightly regulated via multiple mechanisms. Mcl-1 differs from other members of the Bcl-2 family in having a very short half-life. So inhibition
of its expression and/or neutralization of its anti-apoptotic function will rapidly make Mcl-1-dependent cells more susceptible
to apoptosis and provide an opportunity to combat several types of cancers. This review summarizes the current knowledge on
the regulation of Mcl-1 expression and discusses the alternative approaches targeting Mcl-1 in human cancer cells whose survivals
mainly depend on Mcl-1.
Received 6 October 2008; received after revision 21 October 2008; accepted 10 November 2008 相似文献
15.
Porcelli AM Ghelli A Iommarini L Mariani E Hoque M Zanna C Gasparre G Rugolo M 《Cellular and molecular life sciences : CMLS》2008,65(18):2943-2951
Human thyroid carcinoma XTC.UC1 cells harbor a homoplasmic frameshift mutation in the MT-ND1 subunit of respiratory complex
I. When forced to use exclusively oxidative phosphorylation for energy production by inhibiting glycolysis, these cells triggered
a caspase-independent cell death pathway, which was associated to a significant imbalance in glutathione homeostasis and a
cleavage of the actin cytoskeleton. Overexpression of the anti-apoptotic Bcl-2 protein significantly increased the level of
endogenous reduced glutathione, thus preventing its oxidation after the metabolic stress. Furthermore, Bcl-2 completely inhibited
actin cleavage and increased cell adhesion, but was unable to improve cellular viability. Similar effects were obtained when
XTC.UC1 cells were incubated with exogenous glutathione. We hence propose that Bcl-2 can safeguard cytoskeletal stability
through an antioxidant function.
Received 28 May 2008; received after revision 8 July 2008; accepted 29 July 2008 相似文献
16.
Monocytes and their pathophysiological role in Crohn’s disease 总被引:1,自引:1,他引:0
Zhou L Braat H Faber KN Dijkstra G Peppelenbosch MP 《Cellular and molecular life sciences : CMLS》2009,66(2):192-202
Our immune system shows a stringent dichotomy, on the one hand displaying tolerance towards commensal bacteria, but on the
other hand vigorously combating pathogens. Under normal conditions the balance between flora tolerance and active immunity
is maintained via a plethora of dynamic feedback mechanisms. If, however, the balancing act goes faulty, an inappropriate
immune reaction towards an otherwise harmless intestinal flora causes disease, Crohn’s disease for example. Recent developments
in the immunology and genetics of mucosal diseases suggest that monocytes and their derivative cells play an important role
in the pathophysiology of Crohn’s disease. In our review, we summarize the recent studies to discuss the dual function of
monocytes - on the one hand the impaired monocyte function initiating Crohn’s disease, and on the other hand the overactivation
of monocytes and adaptive immunity maintaining the disease. With a view to developing new therapies, both aspects of monocyte
functions need to be taken into account.
Received 1 June 2008; received after revision 24 July 2008; accepted 13 August 2008 相似文献
17.
Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies 总被引:3,自引:0,他引:3
Borrell-Pagès M Zala D Humbert S Saudou F 《Cellular and molecular life sciences : CMLS》2006,63(22):2642-2660
Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary
movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains
a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin.
Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational
modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the
brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood
but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses
on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to
new therapeutic approaches.
Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006 相似文献
18.
A. C. S. Souza S. Azoubel K. C. S. Queiroz M. P. Peppelenbosch C. V. Ferreira 《Cellular and molecular life sciences : CMLS》2009,66(7):1140-1153
Reversible tyrosine phosphorylation is a key posttranslational regulatory modification of proteins in all eukaryotic cells
in normal and pathological processes. Recently a pivotal janus-faced biological role of the low molecular weight protein tyrosine
phosphatase (LMWPTP) has become clear. On the one hand this enzyme is important in facilitating appropriate immune responses
towards infectious agents, on the other hand it mediates exaggerated inflammatory responses toward innocuous stimuli. The
evidence that LMWPTP plays a role in oncological processes has added a promising novel angle. In this review we shall focus
on the regulation of LMWPTP enzymatic activity of signaling pathways of different immunological cells, the relation between
genetic polymorphism of LMWPTP and predisposition to some type of inflammatory disorders and the contribution of this enzyme
to cancer cell onset, growth and migration. Therefore, the LMWPTP is an interesting target for pharmacological intervention,
thus modifying both inappropriate cellular immune responses and cancer cell aggressiveness.
Received 15 August 2008; received after revision 06 October 2008; accepted 14 October 2008 相似文献
19.
Taylor DM Maxwell MM Luthi-Carter R Kazantsev AG 《Cellular and molecular life sciences : CMLS》2008,65(24):4000-4018
Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that target multiple protein substrates to execute diverse biological functions. These enzymes are
key regulators of clinically important cellular and organismal processes, including metabolism, cell division and aging. The
desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven
mammalian sirtuins in less than a decade. The implication of sirtuins in medically important areas such as diabetes, cancer,
cardiovascular dysfunction and neurodegenerative disease has further catapulted them to a prominent status as potential targets
for nutritional and therapeutic development. Here, we present a review of published results on sirtuin biology and its relevance
to human disease.
Received 25 June 2008; received after revision 20 August 2008; accepted 29 August 2008 相似文献
20.
Two major functions of the Golgi apparatus (GA) are formation of complex glycans and sorting of proteins destined for various
subcellular compartments or secretion. To fulfill these tasks proper localization of the accessory proteins within the different
sub-compartments of the GA is crucial. Here we investigate structural determinants mediating transition of the two glycosyltransferases
β-1,4- galactosyltransferase 1 (gal-T1) and the α-1,3-fucosyltransferase 6 (fuc-T6) from the trans-Golgi cisterna to the trans-Golgi network (TGN). Upon treatment with the ionophore monensin both glycosyltransferases are found in TGN-derived swollen
vesicles, as determined by confocal fluorescence microscopy and density gradient fractionation. Both enzymes carry a signal
consisting of the amino acids E5P6 in gal-T1 and D2P3 in fuc-T6 necessary for the transition of these glycosyltransferases from the trans-Golgi cisterna to the TGN, but not for their steady state localization in the trans-Golgi cisterna.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 30 July 2008; received after revision 17 September 2008; accepted 29 September 2008 相似文献