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1.
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
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J. Fitter 《Cellular and molecular life sciences : CMLS》2009,66(10):1672-1681
Most of fundamental studies on protein folding have been performed with small globular proteins consisting of a single domain.
In vitro many of these proteins are well characterized by a reversible two-state folding scheme. However, the majority of proteins
in the cell belong to the class of larger multi-domain proteins that often unfold irreversibly under in vitro conditions. This makes folding studies difficult or even impossible. In spite of these problems for many multi-domain proteins,
folding has been investigated by classical refolding. Co-translational folding of nascent polypeptide chains when synthesized
by ribosomes has also been studied. Single molecule techniques represent a promising approach for future studies on the folding
of multi-domain proteins, and tremendous advances have been made in these techniques in recent years. In particular, fluorescence-based
methods can contribute significantly to an understanding of the fundamental principles of multi-domain protein folding.
Received 3 December 2008; accepted 23 December 2008 相似文献
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Welcome the Family of FANCJ-like Helicases to the Block of Genome Stability Maintenance Proteins 总被引:1,自引:0,他引:1
Y. Wu A. N. Suhasini R. M. Brosh Jr. 《Cellular and molecular life sciences : CMLS》2009,66(7):1209-1222
The FANCJ family of DNA helicases is emerging as an important group of proteins for the prevention of human disease, cancer,
and chromosomal instability. FANCJ was identified by its association with breast cancer, and is implicated in Fanconi Anemia.
Proteins with sequence similarity to FANCJ are important for maintenance of genomic stability. Mutations in genes encoding
proteins related to FANCJ, designated ChlR1 in human and Chl1p in yeast, result in sister chromatid cohesion defects. Nematodes
mutated in dog-1 show germline as well as somatic deletions in genes containing guanine-rich DNA. Rtel knockout mice are embryonic lethal, and embryonic stem cells show telomere loss and chromosomal instability. FANCJ also shares
sequence similarity with human XPD and yeast RAD3 helicases required for nucleotide excision repair. The recently solved structure
of XPD has provided new insight to the helicase core and accessory domains of sequence related Superfamily 2 helicases. The
functions and roles of members of the FANCJ-like helicase family will be discussed.
Received 17 September 2008; received after revision 24 October 2008; accepted 28 October 2008 相似文献
6.
Role of full-length osteoprotegerin in tumor cell biology 总被引:1,自引:1,他引:0
G. Zauli E. Melloni S. Capitani P. Secchiero 《Cellular and molecular life sciences : CMLS》2009,66(5):841-851
Osteoprotegerin (OPG) is a soluble tumor necrosis factor receptor family member, which potently inhibits RANKL-mediated osteoclastogenesis.
Numerous constructs have been created for therapeutic purposes in which the heparin-binding and death homology domains of
OPG were removed and the remaining peptide (amino acids 22–194) was fused to the Fc domain of human IgG1 (OPG-Fc). The administration
of OPG-Fc efficiently counteracted bone loss in a variety of preclinical models of cancers. However, several in vitro studies have shown that native or recombinant full-length OPG not only neuralizes RANKL, but also the death-inducing ligand
TRAIL, suggesting that OPG might potentially counteract the anti-tumor activity of TRAIL. Additional evidence suggests that
full-length OPG possesses RANKL- and TRAIL-independent biological properties, mainly related to the promotion of endothelial
cell survival and angiogenesis. Finally, breast tumor cells overexpressing OPG have shown increased bone metastatic potential
in vivo. The relevance of these apparently conflicting findings in tumor cell biology is highlighted.
Received 2 September 2008; received after revision 29 September 2008; accepted 13 October 2008 相似文献
7.
P. Schläfli E. Borter P. Spielmann R. H. Wenger 《Cellular and molecular life sciences : CMLS》2009,66(5):876-883
The PAS domain kinase PASKIN, also termed PAS kinase or PASK, is an evolutionarily conserved potential sensor kinase related
to the heme-based oxygen sensors of nitrogen-fixing bacteria. In yeast, the two PASKIN homologs link energy flux and protein
synthesis following specific stress conditions. In mammals, PASKIN may regulate glycogen synthesis and protein translation.
Paskin knock-out mice do not show any phenotype under standard animal husbandry conditions. Interestingly, these mice seem to be
protected from the symptoms of the metabolic syndrome when fed a high-fat diet. Energy turnover might be increased in specific
PASKIN-deficient cell types under distinct environmental conditions. According to the current model, binding of a putative
ligand to the PAS domain disinhibits the kinase domain and activates PASKIN auto- and target phosphorylation. Future research
needs to be conducted to elucidate the nature of the putative ligand and the molecular mechanisms of downstream signalling
by PASKIN.
Received 2 November 2008; received after revision 10 December 2008; accepted 5 January 2009 相似文献
8.
H. Riezman A. Munn M. I. Geli L. Hicke 《Cellular and molecular life sciences : CMLS》1996,52(12):1033-1041
Endocytosis is a general term that is used to describe the internalization of external and plasma membrane molecules into the cell interior. In fact, several different mechanisms exist for the internalization step of this process. In this review we emphasize the work on the actin-dependent pathways, in particular in the yeastSaccharomyces cerevisiae, because several components of the molecular machinery are identified. In this yeast, the analysis of endocytosis in various mutants reveals a requirement for actin, calmodulin, a type I myosin, as well as a number of other proteins that affect actin dynamics. Some of these proteins have homology to proteins in animal cells that are believed to be involved in endocytosis. In addition, the demonstration that ubiquitination of some cell surface molecules is required for their efficient internalization is described. We compare the actin, myosin and ubiquitin requirements for endocytosis with recent results found studying these processes usingDictyostelium discoideum and animal cells. 相似文献
9.
D. E. Dye S. Karlen B. Rohrbach O. Staub L. R. Braathen K. A. Eidne D. R. Coombe 《Cellular and molecular life sciences : CMLS》2009,66(4):681-696
hShroom1 (hShrm1) is a member of the Apx/Shroom (Shrm) protein family and was identified from a yeast two-hybrid screen as
a protein that interacts with the cytoplasmic domain of melanoma cell adhesion molecule (MCAM). The characteristic signature
of the Shrm family is the presence of a unique domain, ASD2 (Apx/Shroom domain 2). mRNA analysis suggests that hShrm1 is expressed
in brain, heart, skeletal muscle, colon, small intestine, kidney, placenta and lung tissue, as well a variety of melanoma
and other cell lines. Co-immunoprecipitation and bioluminescence resonance energy transfer (BRET) experiments indicate that
hShrm1 and MCAM interact in vivo and by immunofluorescence microscopy some co-localization of these proteins is observed. hShrm1 partly co-localises with
β-actin and is found in the Triton X-100 insoluble fraction of melanoma cell extracts. We propose that hShrm1 is involved
in linking MCAM to the cytoskeleton.
D. E. Dye, S. Karlen: These authors contributed equally to this work.
Received 09 October 2008; received after revision 23 November 2008; accepted 09 December 2008 相似文献
10.
S. Padilla U. C. Tran M. Jiménez-Hidalgo J. M. López-Martín A. Martín-Montalvo C. F. Clarke P. Navas C. Santos-Ocaña 《Cellular and molecular life sciences : CMLS》2009,66(1):173-186
Coenzyme Q is a lipid molecule required for respiration and antioxidant protection. Q biosynthesis in Saccharomyces cerevisiae requires nine proteins (Coq1p–Coq9p). We demonstrate in this study that Q levels are modulated during growth by its conversion
from demethoxy-Q (DMQ), a late intermediate. Similar conversion was produced when cells were subjected to oxidative stress
conditions. Changes in Q6/DMQ6 ratio were accompanied by changes in COQ7 gene mRNA levels encoding the protein responsible for the DMQ hydroxylation, the penultimate step in Q biosynthesis pathway.
Yeast coq null mutant failed to accumulate any Q late biosynthetic intermediate. However, in coq7 mutants the addition of exogenous Q produces the DMQ synthesis. Similar effect was produced by over-expressing ABC1/COQ8. These results support the existence of a biosynthetic complex that allows the DMQ6 accumulation and suggest that Coq7p is a control point for the Q biosynthesis regulation in yeast.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 04 September 2008; received after revision 22 October 2008; accepted 23 October 2008 相似文献
11.
Methionine adenosyltransferases (MATs) are the family of enzymes that synthesize the main biological methyl donor, S-adenosylmethionine. The high sequence conservation among catalytic subunits from bacteria and eukarya preserves key residues
that control activity and oligomerization, which is reflected in the protein structure. However, structural differences among
complexes with substrates and products have led to proposals of several reaction mechanisms. In parallel, folding studies
begin to explain how the three intertwined domains of the catalytic subunit are produced, and to highlight the importance
of certain intermediates in attaining the active final conformation. This review analyzes the available structural data and
proposes a consensus interpretation that facilitates an understanding of the pathological problems derived from impairment
of MAT function. In addition, new research opportunities directed toward clarification of aspects that remain obscure are
also identified.
Received 22 August 2008; received after revision 22 September 2008; accepted 26 September 2008 相似文献
12.
The continuing disappearance of “pure” Ca2+ buffers 总被引:1,自引:1,他引:0
B. Schwaller 《Cellular and molecular life sciences : CMLS》2009,66(2):275-300
Advances in the understanding of a class of Ca2+-binding proteins usually referred to as “Ca2+ buffers” are reported. Proteins historically embraced within this group include parvalbumins (α and β), calbindin-D9k, calbindin-D28k
and calretinin. Within the last few years a wealth of data has accumulated that allow a better understanding of the functions
of particular family members of the >240 identified EF-hand Ca2+-binding proteins encoded by the human genome. Studies often involving transgenic animal models have revealed that they exert
their specific functions within an intricate network consisting of many proteins and cellular mechanisms involved in Ca2+ signaling and Ca2+ homeostasis, and are thus an essential part of the Ca2+ homeostasome. Recent results indicate that calbindin-D28k, possibly also calretinin and oncomodulin, the mammalian β parvalbumin,
might have additional Ca2+ sensor functions, leaving parvalbumin and calbindin-D9k as the only “pure” Ca2+ buffers.
Received 10 September 2008; received after revision 15 October 2008; accepted 4 November 2008 相似文献
13.
Protein-O-mannosyltransferases (Pmt proteins) catalyse the addition of mannose to serine or threonine residues of secretory proteins.
This modification was described first for yeast and later for other fungi, mammals, insects and recently also for bacteria.
O-mannosylation depends on specific isoforms of the three Pmt1, 2 and 4 subfamilies. In fungi, O-mannosylation determines the structure and integrity of cell walls, as well as cellular differentiation and virulence. O-mannosylation of specific secretory proteins of the human fungal pathogen Candida albicans and of the bacterial pathogen Mycobacterium tuberculosis contributes significantly to virulence. In mammals and insects, Pmt proteins are essential for cellular differentiation and
development, while lack of Pmt activity causes Walker-Warburg syndrome (muscular dystrophy) in humans. The susceptibility
of human cells to certain viruses may also depend on O-mannosyl chains. This review focuses on the various roles of Pmt proteins in cellular differentiation, development and virulence.
Received 6 September 2007; received after revision 3 October 2007; accepted 5 October 2007 相似文献
14.
Plant mitochondrial carriers: an overview 总被引:15,自引:0,他引:15
Laloi M 《Cellular and molecular life sciences : CMLS》1999,56(11-12):918-944
In the two last decades, biochemical studies using mitochondrial swelling experiments or direct solute uptake in isolated mitochondria have lead to the identification of different transport systems at the level of the plant mitochondrial inner membrane. Although most of them have been found to have similar features to those identified in animal mitochondria, some differences have been observed between plant and animal transporters. More recently, molecular biology studies have revealed that most of the mitochondrial exchanges are performed by nuclear encoded proteins, which form a superfamily. Members of this family have been reported in animals, yeast as well as plants. This review attempts to give an overview of the present knowledge concerning the biochemical and molecular characterisation of plant members of the mitochondrial carrier family and, when possible, a comparison with carriers from other organisms. 相似文献
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Large conductance, Ca2+-activated potassium (BK) channels are widely expressed throughout the animal kingdom and play important roles in many physiological
processes, such as muscle contraction, neural transmission and hearing. These physiological roles derive from the ability
of BK channels to be synergistically activated by membrane voltage, intracellular Ca2+ and other ligands. Similar to voltage-gated K+ channels, BK channels possess a pore-gate domain (S5–S6 transmembrane segments) and a voltage-sensor domain (S1–S4). In addition,
BK channels contain a large cytoplasmic C-terminal domain that serves as the primary ligand sensor. The voltage sensor and
the ligand sensor allosterically control K+ flux through the pore-gate domain in response to various stimuli, thereby linking cellular metabolism and membrane excitability.
This review summarizes the current understanding of these structural domains and their mutual interactions in voltage-, Ca2+ - and Mg2+ -dependent activation of the channel.
Received 25 September 2008; received after revision 23 October 2008; accepted 24 October 2008 相似文献
17.
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
18.
Y. Sugano 《Cellular and molecular life sciences : CMLS》2009,66(8):1387-1403
Dye-decolorizing peroxidase (DyP) is produced by a basidiomycete (Thanatephorus cucumeris Dec 1) and is a member of a novel heme peroxidase family (DyP-type peroxidase family) that appears to be distinct from general
peroxidases. Thus far, 80 putative members of this family have been registered in the PeroxiBase database (http://peroxibase.isbsib.ch/)
and more than 400 homologous proteins have been detected via PSI-BLAST search. Although few studies have characterized the
function and structure of these proteins, they appear to be bifunctional enzymes with hydrolase or oxygenase, as well as typical
peroxidase activities. DyP-type peroxidase family suggests an ancient root compared with other general peroxidases because
of their widespread distribution in the living world. In this review, firstly, an outline of the characteristics of DyP from
T. cucumeris is presented and then interesting characteristics of the DyP-type peroxidase family are discussed.
Received 14 October 2008; received after revision 12 November 2008; accepted 17 November 2008 相似文献
19.
Stem cell therapy in stroke 总被引:2,自引:1,他引:1
Locatelli F Bersano A Ballabio E Lanfranconi S Papadimitriou D Strazzer S Bresolin N Comi GP Corti S 《Cellular and molecular life sciences : CMLS》2009,66(5):757-772
Recent work has focused on cell transplantation as a therapeutic option following ischemic stroke, based on animal studies
showing that cells transplanted to the brain not only survive, but also lead to functional improvement. Neural degeneration
after ischemia is not selective but involves different neuronal populations, as well as glial and endothelial cell types.
In models of stroke, the principal mechanism by which any improvement has been observed, has been attributed to the release
of trophic factors, possibly promoting endogenous repair mechanisms, reducing cell death and stimulating neurogenesis and
angiogenesis. Initial human studies indicate that stem cell therapy may be technically feasible in stroke patients, however,
issues still need to be addressed for use in human subjects.
Received 23 June 2008; received after revision 24 September 2008; accepted 30 September 2008 相似文献
20.
T. Hubert S. Grimal P. Carroll A. Fichard-Carroll 《Cellular and molecular life sciences : CMLS》2009,66(7):1223-1238
Collagens are extracellular proteins characterized by a structure in triple helices. There are 28 collagen types which differ
in size, structure and function. Their architectural and functional roles in connective tissues have been widely assessed.
In the nervous system, collagens are rare in the vicinity of the neuronal soma, occupying mostly a “marginal” position, such
as the meninges, the basement membranes and the sensory end organs. In neural development, however, where various ECM molecules
are known to be determinant, recent studies indicate that collagens are no exception, participating in axonal guidance, synaptogenesis
and Schwann cell differentiation. Insights on collagens function in the brain have also been derived from neural pathophysiological
conditions. This review summarizes the significant advances which underscore the function and importance of collagens in the
nervous system.
Received 09 September 2008; received after revision 24 October 2008; accepted 28 October 2008 相似文献