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1.
Leizerman I Avunie-Masala R Elkabets M Fich A Gheber L 《Cellular and molecular life sciences : CMLS》2004,61(16):2060-2070
The kinesin-related protein HsEg5 plays essential roles in mitotic spindle dynamics. Although inhibition of HsEg5 has been suggested as an aid in cancer treatment, the effects of such inhibition on human cells have not been characterized. Here we studied the effects of monastrol, an allosteric HsEg5 inhibitor, on AGS and HT29 cell lines and compared them to those of taxol. While both cell lines were similarly sensitive to taxol, AGS cells were more sensitive to monastrol. The differences in sensitivity were determined by the degree of inhibitory effect on cell proliferation, reversibility of monastrol-induced G2/M arrest, intracellular phenotypes and induction of apoptosis. In both cell lines, monastrol-induced apoptosis was accompanied by mitochondrial membrane depolarization and poly-ADP-ribose polymerase 1 cleavage. In AGS, but not HT29 cells, monastrol-induced apoptosis involved a prominent cleavage of procaspases 8 and 3. While in AGS cells, monastrol induced the formation of symmetric microtubule asters only, in HT29 cells, asymmetric asters were also formed, which may be related to specific HsEg5 functions in HT29 cells.Received 18 February 2004; received after revision 30 May 2004; accepted 16 June 2004 相似文献
2.
Mitotic regulation of the anaphase-promoting complex 总被引:1,自引:1,他引:0
Baker DJ Dawlaty MM Galardy P van Deursen JM 《Cellular and molecular life sciences : CMLS》2007,64(5):589-600
Orderly progression through mitosis is regulated by the anaphase-promoting complex/cyclosome (APC/C), a large multiprotein
E3 ubiquitin ligase that targets key mitotic regulators for destruction by the proteasome. APC/C has two activating subunits,
Cdc20 and Cdh1. The well-established view is that Cdc20 activates APC/C from the onset of mitosis through the metaphase-anaphase
transition, and that Cdh1 does so from anaphase through G1. Recent work, however, indicates that Cdh1 also activates APC/C
in early mitosis and that this APC/C pool targets the anaphase inhibitor securin. To prevent premature degradation of securin,
the nuclear transport factors Nup98 and Rae1 associate with APC/CCdh1-securin complexes. In late metaphase, when all kinetochores are attached to spindle microtubules and the spindle assembly
checkpoint is satisfied, Nup98 and Rae1 are released from these complexes, thereby allowing for prompt ubiquitination of securin
by APC/CCdh1. This, and other mechanisms by which the catalytic activity of APC/C is tightly regulated to ensure proper timing of degradation
of each of its mitotic substrates, are highlighted.
Received 8 October 2006; received after revision 24 November 2006; accepted 8 January 2007 相似文献
3.
Human bystin was identified as a cytoplasmic protein directly binding to trophinin, a cell adhesion molecule potentially involved
in human embryo implantation. Although the trophinin gene is unique to mammals, the bystin gene (BYSL) is conserved across eukaryotes. Recent studies show that bystin plays a key role during the transition from silent trophectoderm
to an active trophoblast upon trophinin-mediated cell adhesion. Bystin gene knockout and knockdown experiments demonstrate
that bystin is essential for embryonic stem cell survival and trophectoderm development in the mouse. Furthermore, biochemical
analysis of bystin in human cancer cells and mouse embryos indicates a function in ribosomal biogenesis, specifically in processing
of 18S RNA in the 40S subunit. Strong evidence that BYSL is a target of c-MYC is consistent with a role for bystin in rapid protein synthesis, which is required for actively growing
cells.
Received 30 June 2007; received after revision 7 August 2007; accepted 29 August 2007 相似文献
4.
Molecular mechanisms of lymphatic vascular development 总被引:8,自引:1,他引:7
Lymphatic vasculature has recently emerged as a prominent area in biomedical research because of its essential role in the
maintenance of normal fluid homeostasis and the involvement in pathogenesis of several human diseases, such as solid tumor
metastasis, inflammation and lymphedema. Identification of lymphatic endothelial specific markers and regulators, such as
VEGFR-3, VEGF-C/D, PROX1, podoplanin, LYVE-1, ephrinB2 and FOXC2, and the development of mouse models have laid a foundation
for our understanding of the major steps controlling growth and remodeling of lymphatic vessels. In this review we summarize
recent advances in the field and discuss how this knowledge as well as use of model organisms, such as zebrafish and Xenopus, should allow further in depth analysis of the lymphatic vascular system.
Received 26 January 2007; received after revision 5 March 2007; accepted 29 March 2007 相似文献
5.
Zazímalová E Krecek P Skůpa P Hoyerová K Petrásek J 《Cellular and molecular life sciences : CMLS》2007,64(13):1621-1637
The PIN-FORMED (PIN) protein family is a group of plant transmembrane proteins with a predicted function as secondary transporters.
PINs have been shown to play a rate-limiting role in the catalysis of efflux of the plant growth regulator auxin from cells,
and their asymmetrical cellular localization determines the direction of cell-to-cell auxin flow. There is a functional redundancy
of PINs and their biochemical activity is regulated at many levels. PINs constitute a flexible network underlying the directional
auxin flux (polar auxin transport) which provides cells in any part of the plant body with particular positional and temporal
information. Thus, the PIN network, together with downstream auxin signalling system(s), coordinates plant development. This
review summarizes recent progress in the elucidation of the role of PIN proteins in polar auxin transport at the cellular
level, with emphasis on their structure and evolution and regulation of their function.
Received 28 December 2006; received after revision 16 February 2007; accepted 26 March 2007 相似文献
6.
Mechanisms of HIV-mediated CD4+ T cell loss leading to immunodeficiency are amongst the most extensively studied yet unanswered
questions in HIV biology. The level of CD4+ T cell depletion in HIV infected patients far exceeds the number of infected T
cells, suggesting an indirect mechanism of HIV pathogenesis termed bystander cell death. Evidence is accumulating that the
HIV envelope glycoprotein (Env) is a major determinant of HIV pathogenesis and plays a critical role in bystander cell death.
The complex structure and function of HIV Env makes the determination of the mechanism of Envmediated apoptosis more complex
than previously thought. This review will examine the complex relationship between HIV Env phenotype, coreceptor expression
and immune activation in determining HIV pathogenesis. We review data here corresponding to the role of HIV Env hemifusion
activity in HIV pathogenesis and how it interplays with other AIDS associated factors such as chemokine receptor expression
and immune activation.
Received 21 March 2008; received after revision 29 April 2008; accepted 30 April 2008 相似文献
7.
Rivera A Mavila A Bayless KJ Davis GE Maxwell SA 《Cellular and molecular life sciences : CMLS》2006,63(12):1425-1439
We were the first to identify cyclin A1 as a p53-induced gene by cDNA expression profiling of p53-sensitive and -resistant
tumor cells [Maxwell S. A. and Davis G. E. (2000) Proc. Natl. Acad. Sci. USA 97, 13009–13014]. We show here that cyclin A1
can induce G2 cell cycle arrest, polyploidy, apoptosis, and mitotic catastrophe in H1299 non-small cell lung, TOV-21G ovarian,
or 786-0 renal carcinoma cells. More cdk1 protein and kinase activities were observed in cyclin A1-induced cells than in GFP
control-induced cells. Thus, cyclin A1 might mediate apoptosis and mitotic catastrophe through an unscheduled or inappropriate
activation of cdk1. Two primary renal cell carcinomas expressing mutated p53 exhibited reduced or absent expression of cyclin
A1 relative to the corresponding normal tissue. Moreover, renal carcinoma-derived mutant p53s were deficient in inducing cyclin
A1 expression in p53-null cells. Cyclin A1 but not cyclin A2 was upregulated in etoposide-treated tumor cells undergoing p53-dependent
apoptosis and mitotic catastrophe. Forced upregulation of cyclin A2 did not induce apoptosis. The data implicate cyclin A1
as a downstream player in p53-dependent apoptosis and G2 arrest.
Received 1 November 2005; received after revision 17 February 2006; accepted 13 April 2006 相似文献
8.
Cbl proteins control multiple cellular processes by acting as ubiquitin ligases and multifunctional adaptor molecules. They are involved in the control of cell proliferation, differentiation and cell morphology, as well as in pathologies such as autoimmune diseases, inflammation and cancer. Here we review recent advances in understanding the role of Cbl and the importance of a growing repertoire of Cbl-interacting proteins in the regulation of signaling pathways triggered by growth factors, antigens, cell adhesion, cytokines and hormones. We also address key issues of the nature of proteins that bind Cbl in particular cells, where they are located, and how they are altered or traffic within cells upon stimulation. It is becoming obvious that temporal and spatial changes in Cbl signaling networks are essential for the control of physiological processes in a variety of cells and organs and that their deregulation can result in the development of human diseases.Received 22 January 2003; received after revision 11 March 2003; accepted 26 March 2003 相似文献
9.
Gonzalez MR Bischofberger M Pernot L van der Goot FG Frêche B 《Cellular and molecular life sciences : CMLS》2008,65(3):493-507
Pore-forming toxins (PFTs) are the most common class of bacterial protein toxins and constitute important bacterial virulence
factors. The mode of action of PFT is starting to be better understood. In contrast, little is known about the cellular response
to this threat. Recent studies reveal that cells do not just swell and lyse, but are able to sense and react to pore formation,
mount a defense, even repair the damaged membrane and thus survive. These responses involve a variety of signal-transduction
pathways and sophisticated cellular mechanisms such as the pathway regulating lipid metabolism. In this review we discuss
the different classes of bacterial PFTs and their modes of action, and provide examples of how the different bacteria use
PFTs. Finally, we address the more recent field dealing with the eukaryotic cell response to PFT-induced damage.
Received 19 September 2007; received after revision 18 October 2007; accepted 23 October 2007 相似文献
10.
Matin A 《Cellular and molecular life sciences : CMLS》2007,64(11):1317-1322
The 129 mouse strain develops congenital testicular germ cell tumors (TGCTs) at a low frequency. TGCTs in mice resemble the
testicular tumors (teratomas) that occur in human infants. The genes that cause these tumors in 129 have not been identified.
The defect at the Ter locus increases TGCT incidence such that 94% of 129-Ter/Ter males develop TGCTs. The primary effect of the Ter mutation is progressive loss of primordial germ cells (PGCs) during embryonic development. This results in sterility in adult
Ter/Ter mice on all mouse strain backgrounds. However, on the 129 background, Ter causes tumor development in addition to sterility. Therefore, Ter acts as a modifier of 129-derived TGCT susceptibility genes. Ter was identified to be a mutation that inactivates the Dead-end1 (Dnd1) gene. In this perspective, I discuss the possible areas of future investigations to elucidate the mechanism of TGCT development
due to Dnd1 inactivation.
Received 29 September 2006; received after revision 29 January 2007; accepted 19 February 2007 相似文献
11.
Complex diseases arise from a combination of heritable and environmental factors. The contribution made by environmental factors
may be mediated through epigenetics. Epigenetics is the study of changes in gene expression that occur without a change in
DNA sequence and are meiotically or mitotically heritable. Such changes in gene expression are achieved through the methylation
of DNA, the post-translational modifications of histone proteins, and RNA-based silencing. Epigenetics has been implicated
in complex diseases such as cancer, schizophrenia, bipolar disorder, autism and systemic lupus erythematosus. The prevalence
and severity of these diseases may be influenced by factors that affect the epigenotype, such as ageing, folate status, in vitro fertilization and our ancestors’ lifestyles. Although our understanding of the role played by epigenetics in complex diseases
remains in its infancy, it has already led to the development of novel diagnostic methods and treatments, which augurs well
for its future health benefits.
Received 6 December 2006; received after revision 29 January 2007; accepted 15 March 2007 相似文献
12.
Phosphatidylinositol 3-kinase (PI3-kinase) activity has been implicated in regulating cell cycle progression at distinct points
in the cell cycle by preventing cell cycle arrest or apoptosis. In this study, the role of PI3-kinase activity during the
entire G1 phase of the ongoing cell cycle was studied in Chinese hamster ovary (CHO) cells synchronized by mitotic shake-off.
We show that inhibition of PI3-kinase activity during and 2 h after mitosis inhibited cell cycle progression into S phase.
In the presence of the PI3-kinase inhibitor wortmannin or LY294002, cells were arrested during early G1 phase, leading to
the expression of the cleaved caspase-3, a central mediator of apoptosis. These results demonstrate that PI3-kinase activity
is required for progression through the M/G1 phase. In the absence of PI3-kinase activity, cells are induced for apoptosis
in this particular phase of the cell cycle.
Received 7 September 2005; received after revision 26 October 2005; accepted 11 November 2005 相似文献
13.
Wu J Feng Y Xie D Li X Xiao W Tao D Qin J Hu J Gardner K Judge SI Li QQ Gong J 《Cellular and molecular life sciences : CMLS》2006,63(21):2538-2545
Cyclin-dependent kinase 1 (CDK1) is a major component of the cell cycle progression engine. Recently, several investigations
provided evidence demonstrating that unscheduled CDK1 activation may also be involved in apoptosis in cancerous cells. In
this article, we demonstrate that X-ray irradiation induced G1 arrest in MOLT-4 lymphocytic leukemia cells, the arrest being
accompanied by reduction in the activity of CDK2, but increased CDK1 activity and cell apoptosis in the G1 phase. Interestingly,
this increase in CDK1 and apoptosis by ionizing radiation was prevented by pretreatment with the CDK1 inhibitor, roscovitine,
suggesting that CDK1 kinase activity is required for radiation-induced apoptotic cell death in this model system. Furthermore,
cyclin B1 and CDK1 were detected co-localizing and associating in G1 phase MOLT-4 cells, with the cellular lysates from these
cells revealing a genotoxic stress-induced increase in CDK1 phosphorylation (Thr-161) and dephosphorylation (Tyr-15), as analyzed
by postsorting immunoprecipitation and immunoblotting. Finally, X-irradiation was found to increase Bcl-2 phosphorylation
in G1 phase cells. Taken together, these novel findings suggest that CDK1 is activated by unscheduled accumulation of cyclin
B1 in G1 phase cells exposed to X-ray, and that CDK1 activation, at the wrong time and in the wrong phase, may directly or
indirectly trigger a Bcl-2-dependent signaling pathway leading to apoptotic cell death in MOLT-4 cells.
Received 30 March 2006; received after revision 23 June 2006; accepted 24 August 2006
J. Wu and Y. Feng contributed equally to this work. 相似文献
14.
Cohausz O Blenn C Malanga M Althaus FR 《Cellular and molecular life sciences : CMLS》2008,65(4):644-655
Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor
(AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR
molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we
determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG),
the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2
and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems
to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.
Received 7 November 2007; received after revision 19 December 2007; accepted 21 December 2007
O. Cohausz, C. Blenn: These two authors contributed equally to this work. 相似文献
15.
Olfactory ensheathing cells have been used in several studies to promote repair in the injured spinal cord. However, cellular
interaction between olfactory ensheathing cells and glial cells induced to be reactive in the aftermath of injury site has
not been investigated. Using an in vitro model of astrogliosis, we show that reactive astrocytes expressed significantly less glial fibrillary acidic protein (GFAP)
when cultured both in direct contact with olfactory ensheathing cells and when the two cell types were separated by a porous
membrane. Immunofluorescence staining also suggested that reactive astrocytes showed decreased chondroitin sulfate proteoglycans
in the presence of olfactory ensheathing cells, although the reduction was not statistically significant. No down-regulation
of GFAP was observed when reactive astrocytes were similarly cultured with Schwann cells. Cell viability assay and bromodeoxyuridine
uptake showed that proliferation of reactive astrocytes was significantly increased in the presence of olfactory ensheathing
cells and Schwann cells.
Received 27 February 2007; received after revision 30 March 2007; accepted 3 April 2007 相似文献
16.
The highly conserved Notch signaling pathway plays pleiotropic roles during embryonic development and is important for the
regulation of selfrenewing tissues. The physiological functions of this signaling cascade range from stem cell maintenance
and influencing cell fate decisions of barely differentiated progenitor cells, to the induction of terminal differentiation
processes, all of which have been found to be recapitulated in different forms of cancers. Although Notch signaling has mostly
been associated with oncogenic and growth-promoting roles, depending on the tissue type it can also function as a tumor suppressor.
Here we describe recent findings on Notch signaling in cancer and tumor angiogenesis, and highlight some of the therapeutic
approaches that are currently being developed to interfere with tumor growth and progression.
Received 2 April 2007; received after revision 29 June 2007; accepted 2 July 2007 相似文献
17.
The recent development of functional models to analyze the early steps of the hepatitis C virus (HCV) life cycle has highlighted
that HCV entry is a slow and complex multistep process involving the presence of several entry factors. Initial host cell
attachment may involve glycosaminoglycans and the low-density lipoprotein receptor, after which the particle appears to interact
sequentially with three entry factors: the scavenger receptor class B type I, the tetraspanin CD81 and the tight-junction
protein claudin-1. Several serum components may also modulate HCV entry, while the recently discovered CD81 partner EWI-2wint
can block the interaction of the viral particle with CD81, potentially preventing infection in the cell types in which it
is expressed. After binding to the host cell, the HCV particle is internalized by clathrin-mediated endocytosis, with fusion
likely occuring in early endosomes. This review summarizes our current knowledge on HCV entry.
Received 27 June 2007; received after revision 2 August 2007; accepted 29 August 2007 相似文献
18.
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
19.
The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified as a key regulator of insulin-dependent
glycogen synthesis. GSK-3 was subsequently shown to function in a wide range of cellular processes including differentiation,
growth, motility and apoptosis. Aberrant regulation of GSK-3 has been implicated in a range of human pathologies including
Alzheimer’s disease, non-insulin-dependent diabetes mellitus (NIDDM) and cancer. As a consequence, the regulation of GSK-3
and the therapeutic potential of GSK-3 inhibitors have become key areas of investigation. This review will focus on the mechanisms
of GSK-3 regulation, with emphasis on modulation by upstream signals, control of substrate specificity and GSK-3 localisation.
The details of these mechanisms will be discussed in the context of specific signalling pathways.
Received 30 January 2007; received after revision 5 March 2007; accepted 16 April 2007 相似文献
20.
A variety of viral-based and immune cell therapies have been proposed for use in the treatment of cancer. One possible approach
to improve the effectiveness of these biological agents may be to combine them such that we can take advantage of natural
immune cell-pathogen relationships. Here we discuss these potential approaches with particular emphasis on the use of immune
cells as carrier vehicles to deliver viral therapies to the tumor.
Received 15 December 2006; received after revision 28 January 2007; accepted 5 March 2007 相似文献