共查询到20条相似文献,搜索用时 31 毫秒
1.
Aniko Keller-Pinter Sandor Bottka Jozsef Timar Janina Kulka Robert Katona Laszlo Dux Ferenc Deak Laszlo Szilak 《Cellular and molecular life sciences : CMLS》2010,67(11):1881-1894
During mitosis, cells detach, and the cell–matrix interactions become restricted. At the completion of cytokinesis, the two
daughter cells are still connected transiently by an intercellular bridge (ICB), which is subjected to abscission, as the
terminal step of cytokinesis. Cell adhesion to the matrix is mediated by syndecan-4 (SDC4) transmembrane heparan sulfate proteoglycan.
Our present work demonstrated that SDC4 promotes cytokinesis in a phosphorylation-dependent manner in MCF-7 breast adenocarcinoma
cells. The serine179-phosphorylation and the ectodomain shedding of SDC4 changed periodically in a cell cycle-dependent way
reaching the maximum at G2/M phases. On the contrary, the phospho-resistant Ser179Ala mutant abrogated the shedding. The phosphorylated
full-length and shed remnants enriched along the mitotic spindles, and subsequently in the ICBs, however, proper membrane
insertion was necessary for midbody localization. Expression of phosphomimicking Ser179Glu SDC4 resulted in incomplete abscission,
whereas expression of the phospho-resistant SDC4 led to giant, multinucleated cells. 相似文献
2.
Regulation of caldesmon activity by Cdc2 kinase plays an important role in maintaining membrane cortex integrity during cell division 总被引:1,自引:0,他引:1
Li Y Wessels D Wang T Lin JL Soll DR Lin JJ 《Cellular and molecular life sciences : CMLS》2003,60(1):198-211
To study the mitosis-specific phosphorylation of caldesmon (CaD), we generated a mutant of the C-terminal fragment (amino
acids 244–538) of human fibroblast CaD (CaD39-6F), as well as a mutant of the full-length CaD (CaD-6F), in which all six potential
phosphorylation sites for Cdc2 kinase were abolished. The mitotic CaD39-6F-overexpressing cells required more time to progress
from anaphase start to 50% cytokinesis, exhibited larger size, and abnormally formed numerous small blebs. In contrast, overexpression
of the wild-type C-terminal fragment of CaD (CaD39) did not result in abnormal bleb formation, but led to larger size and
prolonged the time requirement between anaphase start and 50% cytokinesis. Similar abnormal blebs were also observed in the
CaD-6F-overexpressing cells. CaD-6F-overexpressing cells did not show larger size but required more time to progress from
anaphase start to 50% cytokinesis. These results suggest that mitosis-specific phosphorylation of CaD plays a role in inhibiting
bleb formation and that the N-terminal fragment of CaD is required for cell size determination.
Received 4 September 2002; received after revision 25 November 2002; accepted 4 December 2002 相似文献
3.
Maria C. Shina Annette Müller-Taubenberger Can Ünal Michael Schleicher Michael Steinert Ludwig Eichinger Rolf Müller Rosemarie Blau-Wasser Gernot Glöckner Angelika A. Noegel 《Cellular and molecular life sciences : CMLS》2011,68(2):303-313
Dictyostelium discoideum harbors a short (CRN12) and a long coronin (CRN7) composed of one and two beta-propellers, respectively. They are primarily
present in the cell cortex and cells lacking CRN12 (corA
−) or CRN7 (corB
−) have defects in actin driven processes. We compared the characteristics of a mutant cell line (corA
−
/corB
−) lacking CRN12 and CRN7 with the single mutants focusing on cytokinesis, phagocytosis, chemotaxis and development. Cytokinesis,
uptake of small particles, and developmental defects were not enhanced in the corA
−
/corB
− strain as compared to the single mutants, whereas motility and phagocytosis of yeast particles were more severely impaired.
It appears that although both proteins affect the same processes they do not act in a redundant manner. Rather, they often
act antagonistically, which is in accordance with their proposed roles in the actin cytoskeleton where CRN12 acts in actin
disassembly whereas CRN7 stabilizes actin filaments and protects them from disassembly. 相似文献
4.
Zhang Y Tian Y Chen Q Chen D Zhai Z Shu HB 《Cellular and molecular life sciences : CMLS》2007,64(5):632-640
Polo-like kinase 1 (Plk1) is a highly conserved serine/threonine kinase that plays critical roles in many cell cycle events,
especially in mitosis. In the present study, we identified TTDN1 as a potential interacting partner of Plk1 in yeast two-hybrid
screens. Sequence analysis indicates that TTDN1 contains a consensus Plk1-binding motif at its C terminus. TTDN1 colocalizes
with Plk1 at the centrosome in mitosis and the midbody during cytokinesis. TTDN1 is phosphorylated by Cdk1 in mitosis, and
this is required for its interaction with Plk1. Site-directed mutagenesis indicates that TTDN1 is phosphorylated at multiple
residues, including Ser93 and Ser104. Mutation of Thr120 of TTDN1 abolishes its interaction with Plk1, suggesting phosphorylation
of Thr120 in the consensus Plk1-binding motif is required for its interaction with Plk1. Overexpression of TTDN1 or its knockdown
by siRNA causes multi-polar spindles and multiple nuclei, suggesting that TTDN1 plays a role in regulating mitosis and cytokinesis.
Received 27 November 2006; received after revision 4 January 2007; accepted 25 January 2007
Y. Zhang, Y. Tian: These authors contribute equally to this work. 相似文献
5.
Martínez-Salgado C Rodríguez-Peña AB López-Novoa JM 《Cellular and molecular life sciences : CMLS》2008,65(3):477-492
The mechanisms involved in the development of renal fibrosis are poorly understood. Small Ras GTPases control cell proliferation,
differentiation, cellular growth and apoptosis, with cell-specific expression in the kidney. Cytokines, high glucose medium
or advanced glycation end-products activate Ras in different renal cells. Increased Ras activation has been found in experimental
tubulointerstitial fibrosis. Transforming growth factor-β1 (TGF-β1) and Ras signalling pathways are close related: TGF-β1
overcomes Ras mitogenic effects, and Ras counteracts TGF-β signalling. However, Ras activation is also an intracellular signal
transduction point for several molecules (e.g. TGF-β1) involved in kidney damage. Ras isoforms play different roles in regulating extracellular matrix synthesis in fibroblasts
and mesangial cells. These data give evidence for a role for Ras in renal fibrosis, but no reviews are available on the role
of p21 Ras in this process. Thus, our goal is to review the role of Ras activation and signalling in renal fibrosis.
Received 7 June 2007; received after revision 17 September 2007; accepted 1 October 2007 相似文献
6.
Hoffmeister-Ullerich SA 《Cellular and molecular life sciences : CMLS》2007,64(23):3012-3016
The control of growth and differentiation is a central question not only for developmental biologists but increasingly for
medical research as well. The freshwater polyp hydra was one of the first organisms to be used as a model system for the study
of this question. It was chosen because of its simple body plan and because it is made up of only seven to eight different
cell types. Recent research has shown that despite their simple body plan, cnidarians already exhibit an impressive repertoire
of molecular tools which are responsible for the control of growth and differentiation and amongst which peptides appear to
play an important role.
Received 25 April 2007; received after revision 31 July 2007; accepted 28 August 2007 相似文献
7.
Ramirez F Sakai LY Rifkin DB Dietz HC 《Cellular and molecular life sciences : CMLS》2007,64(18):2437-2446
Fibrillins are the structural components of extracellular microfibrils that impart physical properties to tissues, alone or
together with elastin as elastic fibers. Genetic studies in mice have revealed that fibrillin-rich microfibrils are also involved
in regulating developmental programs and homeostatic processes through the modulation of TGF-β/BMP signaling events. A new
paradigm has thus emerged whereby the spatiotemporal organization of microfibrils dictates both the cellular activities and
physical properties of connective tissues. These observations have paved the way to novel therapeutic approaches aimed at
counteracting the life-threatening complications in human conditions caused by dysfunctions of fibrillin-rich microfibrils.
Received 2 April 2007; received after revision 23 May 2007; accepted 24 May 2007 相似文献
8.
Studies have shown prostaglandin F2α
to be an endogenous tumor promoter in mouse models of skin carcinogenesis; however, the mechanisms by which PGF2α affects cell cycle events remain unknown. Here we performed cell cycle analyses on HEK cells stably expressing the human
FP receptor and found that treatment with PGF2α delays mitosis and is associated with an increased expression of cyclin B1 and Cdc2 kinase activity. In addition, multipolar
spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF2α. Defective cytokinesis was also observed which resulted in gross aneuploidy and polyploidy. Expression of dominant negative
Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF2α. This suggests that FP receptor activation of Rho signaling by PGF2α can interfere with nuclear division. Aneuploidy is associated with genomic instability and may underlie the tumor-promoting
properties of PGF2α.
Received 7 July 2005; received after revision 22 October 2005; accepted 11 November 2005 相似文献
9.
Polyembryonic development, where multiple embryos are formed from a single zygote, evolved at least 15 times in six different
phyla in animals. The mechanisms leading to polyembryony and the forces that shaped the evolution of the polyembryonic developmental
program have remained poorly understood. Recent studies of the polyembryonic development in the endoparasitic wasp Copidosoma floridanum have revealed that the evolution of polyembryony is associated with the evolution of developmental novelties such as total
cleavage, early specification of embryonic and extra-embryonic fates, and a specific cell proliferation phase. These changes
cumulatively result in the formation of thousands of embryos from a single egg. Laser ablation studies and analysis of early
cell fate specification have revealed that a single blastomere representing the progenitor of the primordial germ cell regulates
the proliferation of the embryos. We propose that evolutionary changes in cell cleavage, cell interactions, and the cell-differentiation
program, reminiscent of interactions between the germinal stem cell and stem cell niche in fly ovaries, underlies the evolution
of polyembryony.
Received 30 January 2007; received after revision 21 June 2007; accepted 11 July 2007 相似文献
10.
γ-Secretase is a promiscuous protease that cleaves bitopic membrane proteins within the lipid bilayer. Elucidating both the
mechanistic basis of γ-secretase proteolysis and the precise factors regulating substrate identification is important because
modulation of this biochemical degradative process can have important consequences in a physiological and pathophysiological
context. Here, we briefly review such information for all major classes of intramembranously cleaving proteases (I-CLiPs),
with an emphasis on γ-secretase, an I-CLiP closely linked to the etiology of Alzheimer’s disease. A large body of emerging
data allows us to survey the substrates of γ-secretase to ascertain the conformational features that predispose a peptide
to cleavage by this enigmatic protease. Because substrate specificity in vivo is closely linked to the relative subcellular compartmentalization of γ-secretase and its substrates, we also survey the
voluminous body of literature concerning the traffic of γ-secretase and its most prominent substrate, the amyloid precursor
protein.
Received 4 October 2007; received after revision 1 December 2007; accepted 7 December 2007 相似文献
11.
Courtois G 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1123-1132
CYLD is a protein with tumor suppressor properties which was originally discovered associated with cylindromatosis, an inherited
cancer exclusively affecting the folicullo-sebaceous-apocrine unit of the epidermis. CYLD exhibits deubiquitinating activity
and acts as a negative regulator of NF-κB and JNK signaling through its interaction with NEMO and TRAF2. Recent data suggest
that this is unlikely to be its unique function in vivo. CYLD has also been shown to control other seemingly disparate cellular processes, such as proximal T cell receptor signaling,
TrkA endocytosis and mitosis. In each case, this enzyme appears to act by regulating a specific type of polyubiquitination,
K63 polyubiquitination, that does not result in recognition and degradation of proteins by the proteasome but instead controls
their activity through diverse mechanisms.
Received 6 October 2007; received after revision 2 November 2007; accepted 23 November 2007 相似文献
12.
Emerging roles of the SUMO pathway in development 总被引:1,自引:1,他引:0
13.
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
14.
Hurtaud C Gelly C Chen Z Lévi-Meyrueis C Bouillaud F 《Cellular and molecular life sciences : CMLS》2007,64(14):1853-1860
Uncoupling protein 2 (UCP2) belongs to a family of transporters/exchangers of the mitochondrial inner membrane. Using cell
lines representing natural sites of UCP2 expression (macrophages, colonocytes, pancreatic beta cells), we show that UCP2 expression
is stimulated by glutamine at physiological concentrations. This control is exerted at the translational level. We demonstrate
that the upstream open reading frame (ORF1) in the 5’ untranslated region (5’UTR) of the UCP2 mRNA is required for this stimulation
to take place. Cloning of the 5’ UTR of the UCP2 mRNA in front of a GFP cDNA resulted in a reporter gene with which GFP expression
could be induced by glutamine. An effect of glutamine on translation of a given mRNA has not been identified before, and this
is the first evidence for a link between UCP2 and glutamine, an amino acid oxidized by immune cells or intestinal epithelium
and playing a role in the control of insulin secretion.
Received 26 January 2007; received after revision 16 April 2007; accepted 8 May 2007
C. Hurtaud, C. Gelly: These authors contributed equally to this work. 相似文献
15.
Computational inhibitor design against malaria plasmepsins 总被引:1,自引:1,他引:0
Bjelic S Nervall M Gutiérrez-de-Terán H Ersmark K Hallberg A Aqvist J 《Cellular and molecular life sciences : CMLS》2007,64(17):2285-2305
Plasmepsins are aspartic proteases involved in the degradation of the host cell hemoglobin that is used as a food source by
the malaria parasite. Plasmepsins are highly promising as drug targets, especially when combined with the inhibition of falcipains
that are also involved in hemoglobin catabolism. In this review, we discuss the mechanism of plasmepsins I–IV in view of the
interest in transition state mimetics as potential compounds for lead development. Inhibitor development against plasmepsin
II as well as relevant crystal structures are summarized in order to give an overview of the field. Application of computational
techniques, especially binding affinity prediction by the linear interaction energy method, in the development of malarial
plasmepsin inhibitors has been highly successful and is discussed in detail. Homology modeling and molecular docking have
been useful in the current inhibitor design project, and the combination of such methods with binding free energy calculations
is analyzed.
S. Bjelic, M. Nervall: These authors contributed equally to this work.
Received 27 February 2007; received after revision 17 April 2007; accepted 26 April 2007 相似文献
16.
Williams AE 《Cellular and molecular life sciences : CMLS》2008,65(4):545-562
MicroRNAs (miRNAs) are a recently discovered family of small regulatory molecules that function by modulating protein production.
There are approximately 500 known mammalian miRNA genes, and each miRNA may regulate hundreds of different protein-coding
genes. Mature miRNAs bind to target mRNAs in a protein complex known as the miRNA-induced silencing complex (miRISC), sometimes
referred to as the miRNP (miRNA-containing ribonucleoprotein particles), where mRNA translation is inhibited or mRNA is degraded.
These actions of miRNAs have been shown to regulate several developmental and physiological processes including stem cell
differentiation, haematopoiesis, cardiac and skeletal muscle development, neurogenesis, insulin secretion, cholesterol metabolism
and the immune response. Furthermore, aberrant expression has been implicated in a number of diseases including cancer and
heart disease. The role of miRNAs in these developmental, physiological and pathological processes will be reviewed.
Received 3 August 2007; received after revision 3 October 2007; accepted 5 October 2007 相似文献
17.
The compositional difference in microbial and human cell membranes allows antimicrobial peptides to preferentially bind microbes.
Peptides which specifically target lipopolysaccharide (LPS) and palmitoyl-oleoyl-phosphatidylglycerol (POPG) are efficient
antibiotics. From the core LPS-binding region of Factor C, two 34-mer Sushi peptides, S1 and S3, were derived. S1 functions
as a monomer, while S3 is active as a dimer. Both S1 and S3 display detergent-like properties in disrupting LPS aggregates,
with specificity for POPG resulting from electrostatic and hydrophobic forces between the peptides and the bacterial lipids.
During interaction with POPG, the S1 transitioned from a random coil to an α-helix, while S3 resumed a mixture of α-helix
and β-sheet structures. The unsaturated nature of POPG confers fluidity and enhances insertion of the peptides into the lipid
bilayer, causing maximal disruption of the bacterial membrane. These parameters should be considered in designing and developing
new generations of peptide antibiotics with LPS-neutralizing capability.
Received 2 October 2007; received after revision 2 November 2007; accepted 4 December 2007
J. L. Ding, B. Ho: Co-senior authors. 相似文献
18.
Strell C Lang K Niggemann B Zaenker KS Entschladen F 《Cellular and molecular life sciences : CMLS》2007,64(24):3306-3316
The extravasation of leukocytes and tumor cells is a multi-step process with the involvement of various adhesion molecules
depending on the three steps rolling, adhesion, and diapedesis. We have developed an in vitro model, by which we investigated the rolling and adhesion of neutrophil granulocytes and MDA-MB-468 human breast carcinoma
cells to lung endothelial cells under physiological flow-conditions. We found that norepinephrine had an inhibitory function
on the fMLP-promoted adhesion of neutrophil granulocytes due to a down-regulation of β2-integrin. Furthermore, neutrophil
granulocytes serve as linking cells for the interaction of the MDA-MB-468 cells with the endothelium, which are both β2-integrin
negative, but express the β2-integrin ligand ICAM-1. In addition, we show here that N-cadherin is up-regulated on the endothelial
cells and on neutrophil granulocytes in response to fMLP. This up-regulation resulted in a significant increase of adherent
MDA-MB-468 cells, which are also N-cadherin positive.
Received 3 September 2007; received after revision 17 October 2007; accepted 22 October 2007 相似文献
19.
Viero G Gropuzzo A Joubert O Keller D Prévost G Dalla Serra M 《Cellular and molecular life sciences : CMLS》2008,65(2):312-323
γ-Hemolysins are pore-forming toxins which develop from water-soluble monomers by combining two different ‘albeit homologous’
proteins. They form oligomeric pores in both cell and model membranes by undergoing a still poorly understood conformational
rearrangement in the stem region. The stem is formed by three β-strands, folded onto the core of the soluble protein and completely
extended in the pore. We propose a new model to explain such a process. Seven double-cysteine mutants were developed by inserting
one cysteine on the stretch that links the β-hairpin to the core of the protein and another on different positions along the
β-strands. The membrane bound protein was blocked in a non-lytic state by S–S bond formation. Six mutants were oxidized as
inactive intermediates, but became active after adding DTT. These results demonstrate that the stem extension can be temporarily
frozen and that the β-barrel formation occurs by β-strand concerted step-by-step sliding.
Received 22 October 2007; received after revision 15 November 2007; accepted 19 November 2007 相似文献