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1.
Shikanai T 《Cellular and molecular life sciences : CMLS》2006,63(6):698-708
In plants, RNA editing is a process for converting a specific nucleotide of RNA from C to U and less frequently from U to
C in mitochondria and plastids. To specify the site of editing, the cis-element adjacent to the editing site functions as a binding site for the trans-acting factor. Genetic approaches using Arabidopsis thaliana have clarified that a member of the protein family with pentatricopeptide repeat (PPR) motifs is essential for RNA editing
to generate a translational initiation codon of the chloroplast ndhD gene. The PPR motif is a highly degenerate unit of 35 amino acids and appears as tandem repeats in proteins that are involved
in RNA maturation steps in mitochondria and plastids. The Arabidopsis genome encodes approximately 450 members of the PPR family, some of which possibly function as trans-acting factors binding the cis-elements of the RNA editing sites to facilitate access of an unidentified RNA editing enzyme. Based on this breakthrough
in the research on plant RNA editing, I would like to discuss the possible steps of co-evolution of RNA editing events and
PPR proteins.
Received 30 September 2005; received after revision 5 November 2005; accepted 28 November 2005 相似文献
2.
Melanocortin receptors: their functions and regulation by physiological agonists and antagonists 总被引:14,自引:0,他引:14
Abdel-Malek ZA 《Cellular and molecular life sciences : CMLS》2001,58(3):434-441
The melanocortins are a family of bioactive peptides derived from proopiomelanocortin, and share significant structural similarity.
Those peptides are best known for their stimulatory effects on pigmentation and steroidogenesis. Melanocortins are synthesized
in various sites in the central nervous system and in peripheral tissues, and participate in regulating multiple physiological
functions. Research during the past decade has provided evidence that melanocortins elicit their diverse biological effects
by binding to a distinct family of G protein-coupled receptors with seven transmembrane domains. To date, five melanocortin
receptor genes have been cloned and characterized. Those receptors differ in their tissue distribution and in their ability
to recognize the various melanocortins and the physiological antagonists, agouti signaling protein and agouti-related protein.
These advances have opened new horizons for exploring the significance of melanocortins, their antagonists, and their receptors
in a variety of important physiological functions.
Received 5 October 2000; accepted 10 November 2000 相似文献
3.
The BAG (Bcl-2 associated athanogene) family is a multifunctional group of proteins that perform diverse functions ranging from apoptosis to tumorigenesis.
An evolutionarily conserved group, these proteins are distinguished by a common conserved region known as the BAG domain.
BAG genes have been found in yeasts, plants, and animals, and are believed to function as adapter proteins forming complexes
with signaling molecules and molecular chaperones. In humans, a role for BAG proteins has been suggested in carcinogenesis,
HIV infection, and Parkinson’s disease. These proteins are therefore potential therapeutic targets, and their expression in
cells may serve as a predictive tool for such diseases. In plants, the Arabidopsis thaliana genome contains seven homologs of the BAG family, including four with domain organization similar to animal BAGs. Three members
contain a calmodulin-binding domain possibly reflecting differences between plant and animal programmed cell death. This review
summarizes current understanding of BAG proteins in both animals and plants.
Received 21 November 2007; received after revision 17 December 2007; accepted 2 January 2008 相似文献
4.
This review describes the structure and function of prolyl endopeptidase (PEP) enzymes and how they are being evaluated as
drug targets and therapeutic agents. The most well studied PEP family has a two-domain structure whose unique seven-blade
β-propeller domain works with the catalytic domain to hydrolyze the peptide bond on the carboxyl side of internal proline
residues of an oligopeptide substrate. Structural and functional studies on this protease family have elucidated the mechanism
for peptide entry between the two domains. Other structurally unrelated PEPs have been identified, but have not been studied
in detail. Human PEP has been evaluated as a pharmacological target for neurological diseases due to its high brain concentration
and ability to cleave neuropeptides in vitro. Recently, microbial PEPs have been studied as potential therapeutics for celiac sprue, an inflammatory disease of the small
intestine triggered by proline-rich gluten.
Received 6 July 2006; received after revision 17 August 2006; accepted 1 November 2006 相似文献
5.
Wikenheiser-Brokamp KA 《Cellular and molecular life sciences : CMLS》2006,63(7-8):767-780
The retinoblastoma (Rb) gene was identified as the first tumor suppressor gene two decades ago. Since this initial discovery,
it has become clear that deregulated Rb function constitutes a hallmark of human malignancies. Rb is a well-established regulator
of the cell cycle. Rb has also been implicated in playing a role in a wide variety of cellular processes including DNA repair,
cellular senescence, cell fate determination and apoptosis. Animals lacking Rb and/or its family members p107 and p130 have
led scientists to uncover new and exciting roles for this protein family in development as well as tumor suppression. The
ability to ablate Rb in a temporal and cell-type-specific manner has offered further, often unexpected, insights into Rb function.
This review summarizes the phenotypic consequences of Rb family ablation in mice, and discusses how these findings contribute
to the increasingly complex picture of Rb family function in development and tumor suppression.
Received 11 October 2005; received after revision 16 November 2005; accepted 28 November 2005 相似文献
6.
Function and molecular evolution of multicopper blue proteins 总被引:1,自引:0,他引:1
Multicopper blue proteins (MCBPs) are multidomain proteins that utilize the distinctive redox ability of copper ions. There are a variety of MCBPs that have been roughly classified into three different groups, based on their domain organization and functions: (i) nitrite reductase-type with two domains, (ii) laccase-type with three domains, and (iii) ceruloplasmin-type with six domains. Together, the second and third group are often commonly called multicopper oxidases (MCOs). The rapid accumulation of genome sequence information in recent years has revealed several new types of proteins containing MCBP domains, mainly from bacteria. In this review, the recent research on the functions and structures of MCBPs is summarized, mainly focusing on the new types. The latter half of this review focusses on the twodomain MCBPs, which we propose as the evolutionary intermediate of the MCBP family.Received 25 February 2005; received after revision 23 May 2005; accepted 31 May 2005 相似文献
7.
Juste M Martin-Eauclaire MF Devaux C Billiald P Aubrey N 《Cellular and molecular life sciences : CMLS》2007,64(2):206-218
In recent years, several molecular engineering methods of designing bispecific antibodies in various formats have been developed.
Tandem-scFvs comprising two scFvs fused together via a peptide are 55-kDa molecules, and are one of the most promising and
most straightforward approaches to bispecific antibody production. We report an attempt to design more effective antivenoms
to the Androctonus australis scorpion using murine scFvs as building blocks to create a unique bispecific molecule that neutralizes the potent neurotoxins
AahI and AahII. The tandem-scFv was produced in recombinant bacteria, purified by immobilized metal ion affinity chromatography, and analyzed
by polyacrylamide gel electrophoresis, Western blot, gel filtration, mass spectrometry, and direct and competitive radioimmunoassay.
In vivo, it neutralized the binding of the AahI and AahII toxins to their receptor, and protected mice against experimental envenomation. The findings reported here highlight the
potential of recombinant antibody fragments for protecting against scorpion venom toxicity.
Received 8 September 2006; received after revision 10 November 2006; accepted 27 November 2006 相似文献
8.
Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain 总被引:1,自引:0,他引:1
Rivera-Milla E Stuermer CA Málaga-Trillo E 《Cellular and molecular life sciences : CMLS》2006,63(3):343-357
Reggies (flotillins) are detergent-resistant microdomains involved in the scaffolding of large heteromeric complexes that
signal across the plasma membrane. Based on the presence of an evolutionarily widespread motif, reggies/flotillins have been
included within the SPFH (stomatin-prohibitin-flotillin-HflC/K) protein superfamily. To better understand the origin and evolution
of reggie/flotillin structure and function, we searched databases for reggie/flotillin and SPFH-like proteins in organisms
at the base and beyond the animal kingdom, and used the resulting dataset to compare their structural and functional domains.
Our analysis shows that the SPFH grouping has little phylogenetic support, probably due to convergent evolution of its members.
We also find that reggie/flotillin homologues are highly conserved among metazoans but are absent in plants, fungi and bacteria,
where only proteins with ‘reggie-like’ domains can be found. However, despite their low sequence similarities, reggie/flotillin
and ‘reggie-like’ domains appear to subserve related functions, suggesting that their basic biological role was acquired independently
during evolution.
Received 21 September 2005; received after revision 14 November 2005; accepted 21 November 2005 相似文献
9.
Flavodoxins: sequence, folding, binding, function and beyond 总被引:5,自引:0,他引:5
Sancho J 《Cellular and molecular life sciences : CMLS》2006,63(7-8):855-864
Flavodoxins are electron-transfer proteins involved in a variety of photosynthetic and non-photosynthetic reactions in bacteria,
whereas, in eukaryotes, a descendant of the flavodoxin gene helps build multidomain proteins. The redox activity of flavodoxin
derives from its bound flavin mononucleotide cofactor (FMN), whose intrinsic properties are profoundly modified by the host
apoprotein. This review covers the very exciting last decade of flavodoxin research, in which the folding pathway, the structure
and stability of the apoprotein, the mechanism of FMN recognition, the interactions that stabilize the functional complex
and tailor the redox potentials, and many details of the binding and electron transfer to partner proteins have been revealed.
The next decade should witness an even deeper understanding of the flavodoxin molecule and a greater comprehension of its
many physiological roles. The fact that flavodoxin is essential for the survival of some human pathogens could make it a drug
target on its own.
Received 26 October 2005; received after revision 20 November 2005; accepted 14 December 2005 相似文献
10.
Bleifuss E Kammertoens T Hutloff A Quarcoo D Dorner M Straub P Uckert W Hildt E 《Cellular and molecular life sciences : CMLS》2006,63(5):627-635
Cell-penetrating peptides (CPPs) have been shown to improve antigen loading of dendritic cell vaccines. Here we asked whether
fusion of a CPP to a protein improves its immunogenicity when this fusion protein is directly applied as vaccine. We used
the cell-penetrating translocation motif (TLM) derived from the hepatitis B virus, because no size limitation of cargos has
been observed. Increased immunogenicity was observed when TLM was fused to ovalbumin (TLM-ova). TLM-ova was found to be superior
to ova in inducing proliferation and cytotoxicity of ova-specific CD8+ T cells in vitro and in vivo. Using ovalbumin-expressing thymoma cells (EG7-ova), an improved anti-tumor immune response was observed for TLM-ova vaccination
versus vaccination with ova. Moreover, TLM-ova vaccination induced a higher titer of anti-ovalbumin IgG2a antibodies compared
to ova. These data demonstrate that CPP-protein vaccines can improve cellular as well as humoral immune responses.
Received 16 November 2005; received after revision 12 December 2005; accepted 10 January 2006
†These authors contributed equally to this work 相似文献
11.
Staphylococci have two mechanisms for resistance to β-lactam antibiotics. One is the production of β-lactamases, enzymes that
hydrolytically destroy β-lactams. The other is the expression of penicillin-binding protein 2a (PBP 2a), which is not susceptible
to inhibition by β-lactam antibiotics. Strains of S. aureus exhibiting either β-lactamase or PBP 2a-directed resistance (or both) have established a considerable ecological niche among
human pathogens. The emergence and subsequent spread of bacterial strains designated as methicillin-resistant S. aureus (MRSA), from the 1960s to the present, has created clinical difficulties for nosocomial treatment on a global scale. The
recent variants of MRSA that are resistant to glycopeptide antibiotics (such as vancomycin) have ushered in a new and disconcerting
chapter in the evolution of this organism.
Received 2 April 2005; received after revision 15 July 2005; accepted 25 July 2005 相似文献
12.
The integrin family of extracellular matrix receptors regulates many aspects of cell life, in particular cell adhesion and migration. These two processes depend on organization of the actin cytoskeleton into adhesive and protrusive organelles in response to extracellular signals. Integrins are important switch points for the spatiotemporal control of actin-based motility in higher eukaryotes. Ligands of integrin cytoplasmic tails are central elements of signalling pathways involving small GTPases as well as protein and lipid kinases in the regulation of Factin crosslinking, actin treadmilling and de novo nucleation of actin filaments. We present an overview of common pathways and discuss recent evidence for their differential use by individual integrin receptors.Received 24 November 2004; received after revision 17 January 2005; accepted 19 January 2005 相似文献
13.
H. Van Dael 《Cellular and molecular life sciences : CMLS》1998,54(11):1217-1230
Protein folding is an extremely active field of research where biology, chemistry, computer science and physics meet. Although
the study of protein-folding intermediates in general and equilibrium intermediates in particular has grown considerably in
recent years, many questions regarding the conformational state and the structural features of the various partially folded
intermediate states remain unanswered. Performing kinetic measurements on proteins that have had their structures modified
by site-directed mutagenesis, the so-called protein-engineering method, is an obvious way to gain fine structural information.
In the present review, this method has been applied to a variety of proteins belonging to the lysozyme/α-lactalbumin family. Besides recombinants obtained by point mutations of individual critical residues, chimeric proteins in
which whole structural elements (10 – 25 residues) from α-lactalbumin were inserted into a human lysozyme matrix are examined. The conformational properties of the equilibrium intermediate
states are discussed together with the structural characterization of the partially unfolded states encountered in the kinetic
folding pathway.
Received 28 May 1998; received after revision 6 July 1998; accepted 6 July 1998 相似文献
14.
Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product Calcipressin 1 (or RCAN1) in disease 总被引:5,自引:0,他引:5
The DSCR1 (Adapt78) gene1 is transiently induced by stresses to temporarily protect cells against further potentially lethal challenges. However, chronic
expression of the DSCR1 (Adapt78) gene has now been implicated in several pathological conditions including Alzheimer’s disease, Down syndrome and cardiac
hypertrophy. Calcipressin 1 has been shown to function through direct binding and inhibition of the serine threonine protein
phosphatase Calcineurin. Pharmacological inhibition of calcineurin, by the immunosuppressive drugs cyclosporin A and FK506,
affects a wide variety of diseases. It is, therefore, likely that this endogenous calcineurin inhibitor, calcipressin 1, may
also play a role in a variety of human diseases.
1Please note that the mammalian DSCR1 gene is also called Adapt78 or RCAN1, and its protein products have been named Calcipressin1, MCIP1 and RCAN1. A proposal to adopt a single gene name of RCAN1 and a protein name RCAN1 (for Regulator of Calcineurin) has been endorsed by the HUGO Gene Nomenclature Committee, but final
approval must await agreement from a majority of researchers in the field.
Received 2 March 2005; received after revision 27 May 2005; accepted 19 July 2005 相似文献
15.
Lonez C Legat A Vandenbranden M Ruysschaert JM 《Cellular and molecular life sciences : CMLS》2008,65(4):620-630
The inflammatory effect of unmethylated CpG DNA sequences represents a major obstacle to the use of cationic lipids for in vivo gene therapy. Although the mechanism of CpG-induced inflammatory response is rather well understood nowadays, few solutions
have been designed to circumvent this effect in gene therapy experiments. Our previous work has shown that a refractory state
towards inflammation can be elicited by preinjecting cationic liposomes. Here, we present evidence that diC14-amidine liposomes
confer new anti-inflammatory properties to phospholipids from low-density lipoprotein (LDL) and even to synthetic phospholipids
for which such an observation has not been reported so far. Whereas oxidation of LDL lipids was a prerequisite for any anti-inflammatory
activity, lipid oxidation is no longer required in our experiments, suggesting that cationic lipids transport phospholipids
through a different route and affect different pathways.This opens up new possibilities for manipulating inflammatory responses
in gene therapy protocols but also in a general manner in immunological experiments.
Received 12 November 2007; received after revision 4 December 2007; accepted 4 December 2007 相似文献
16.
Morrison BE Majdzadeh N D'Mello SR 《Cellular and molecular life sciences : CMLS》2007,64(17):2258-2269
Neurodegenerative disease strikes millions worldwide and there is mounting evidence suggesting that underlying the onset and
progression of these debilitating diseases is inappropriate neuronal apoptosis. Recent reports have implicated a family of
proteins known as histone deacetylases (HDACs) in various neuronal processes including the neuronal death program. Initial
headway in this field has been made largely through the use of broad-spectrum HDAC inhibitors. In fact, pharmacological inhibition
of HDAC activity has been shown to protect neurons in several models of neurodegeneration. The observation that HDAC inhibitors
can have opposing effects in different paradigms of neurodegeneration suggests that individual members of the HDAC protein
family may play distinct roles that could depend on the specific cell type under study. The purpose of this review is to detail
work involving the use of HDAC inhibitors within the context of neurodegeneration and examine the roles of individual HDAC
members in the nervous system with specific focus on neuronal cell death.
Received 25 January 2007; received after revision 3 April 2007; accepted 26 April 2007 相似文献
17.
The structure and function of heterotrimeric G protein subunits is known in considerable detail. Upon stimulation of a heptahelical
receptor by the appropriate agonists, the cognate G proteins undergo a cycle of activation and deactivation; the α-subunits and the βγ-dimers interact sequentially with several reaction partners (receptor, guanine nucleotides and effectors as well as regulatory
proteins) by exposing appropriate binding sites. For most of these domains, low molecular weight ligands have been identified
that either activate or inhibit signal transduction. These ligands include short peptides derived from receptors, G protein
subunits and effectors, mastoparan and related insect venoms, modified guanine nucleotides, suramin analogues and amphiphilic
cations. Because compounds that act on G proteins may be endowed with new forms of selectivity, we propose that G protein
subunits may therefore be considered as potential drug targets.
Received 18 September 1998; received after revision 6 November 1998; accepted 11 November 1998 相似文献
18.
The Hedgehog family of growth factors activate a highly conserved signaling system for cell-cell communication that regulates
cell proliferation and differentiation during development. Abnormal activation of the Hedgehog pathway has been demonstrated
in a variety of human tumors, including those of the skin, brain, lung and digestive tract. Hedgehog pathway activity in these
tumors is required for cancer cell proliferation and tumor growth. Recent studies have uncovered the role for Hedgehog signaling
in advanced prostate cancer and demonstrated that autocrine signaling by tumor cells is required for proliferation, viability,
and invasive behavior. The level of Hedgehog activity correlates with the severity of the tumor and is both necessary and
sufficient for metastatic behavior. Blockade of Hedgehog signaling leads to tumor shrinkage and remission in preclinical tumor
xenograft models. Thus, Hedgehog signaling represents a novel pathway in prostate cancer that offers opportunities for prognostic
biomarker development, drug targeting and therapeutic response monitoring.
Received 18 August 2005; received after revision 30 September 2005; accepted 1 November 2005 相似文献
19.
Galectin-7 总被引:4,自引:0,他引:4
Galectins are a family of animal lectins with an affinity for β-galactosides. They are differentially expressed by various
tissues and appear to be functionally multivalent, exerting a wide range of biological activities both during development
and in adult tissue. Galectin-7, a member of this family, contributes to different events associated with the differentiation
and development of pluristratified epithelia. It is also associated with epithelial cell migration, which plays a crucial
role in the re-epithelialization process of corneal or epidermal wounds. In addition, recent evidence indicates that galectin-7,
designated as the product of the p53-induced gene 1 (PIG1), is a regulator of apoptosis through JNK activation and mitochondrial
cytochrome c release. Defects in apoptosis constitute one of the major hallmarks of human cancers, and galectin-7 can act
as either a positive or a negative regulatory factor in tumour development, depending on the histological type of the tumour.
Received 30 October 2005; received after revision 15 November 2005; accepted 25 November 2005 相似文献
20.
Transient receptor potential (TRP) ion channels have been identified as cellular sensors responding to diverse external and
internal stimuli. This review will cover the TRPV subfamily that comprises vertebrate and invertebrate members. The six mammalian
TRPV channels were demonstrated to function in thermosensation, mechanosensation, osmosensation and Ca2+ uptake. Invertebrate TRPV channels, five in Caenorhabditis elegans and two in Drosophila, have been shown to play a role in mechanosensation, such as hearing and proprioception in Drosophila and nose touch in C. elegans, and in the response to osmotic and chemical stimuli in C. elegans. We will focus here on the role that TRPV ion channels play in mechanosensation and a related sensory (sub-)modality, osmosensation.
Received 2 May 2005; received after revision 30 July 2005; accepted 30 August 2005 相似文献