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101.
102.
Gauthier LR Granotier C Hoffschir F Etienne O Ayouaz A Desmaze C Mailliet P Biard DS Boussin FD 《Cellular and molecular life sciences : CMLS》2012,69(4):629-640
Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways.
Replication is a critical period for telomeres because of the requirement for reconstitution of functional protected telomere
conformations, a process that involves DNA repair proteins. Using knockdown of DNA-PKcs and Rad51 expression in three different
cell lines, we demonstrate the respective involvement of NHEJ and HR in the formation of telomere aberrations induced by the
G-quadruplex ligand 360A during or after replication. HR contributed to specific chromatid-type aberrations (telomere losses
and doublets) affecting the lagging strand telomeres, whereas DNA-PKcs-dependent NHEJ was responsible for sister telomere
fusions as a direct consequence of G-quadruplex formation and/or stabilization induced by 360A on parental telomere G strands.
NHEJ and HR activation at telomeres altered mitotic progression in treated cells. In particular, NHEJ-mediated sister telomere
fusions were associated with altered metaphase-anaphase transition and anaphase bridges and resulted in cell death during
mitosis or early G1. Collectively, these data elucidate specific molecular and cellular mechanisms triggered by telomere targeting
by the G-quadruplex ligand 360A, leading to cancer cell death. 相似文献
103.
Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of
calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded
in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels
is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and
interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current
state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and
internalization of this important ion channel family. 相似文献
104.
Although all nucleated cells within a multicellular organism contain a complete copy of the genome, cell identity relies on
the expression of a specific subset of genes. Therefore, when cells divide they must not only copy their genome to their daughters,
but also ensure that the pattern of gene expression present before division is restored. While the carrier of this epigenetic
memory has been a topic of much research and debate, post-translational modifications of histone proteins have emerged in
the vanguard of candidates. In this paper we examine the mechanisms by which histone post-translational modifications are
propagated through DNA replication and cell division, and we critically examine the evidence that they can also act as vectors
of epigenetic memory. Finally, we consider ways in which epigenetic memory might be disrupted by interfering with the mechanisms
of DNA replication. 相似文献
105.
Rai A Nöthe H Tzvetkov N Korenbaum E Manstein DJ 《Cellular and molecular life sciences : CMLS》2011,68(16):2751-2767
Dictyostelium discoideum cells produce five dynamin family proteins. Here, we show that dynamin B is the only member of this group of proteins that
is initially produced as a preprotein and requires processing by mitochondrial proteases for formation of the mature protein.
Our results show that dynamin B-depletion affects many aspects of cell motility, cell-cell and cell-surface adhesion, resistance
to osmotic shock, and fatty acid metabolism. The mature form of dynamin B mediates a wide range and unique combination of
functions. Dynamin B affects events at the plasma membrane, peroxisomes, the contractile vacuole system, components of the
actin-based cytoskeleton, and cell adhesion sites. The modulating effect of dynamin B on the activity of the contractile vacuole
system is unique for the Dictyostelium system. Other functions displayed by dynamin B are commonly associated with either classical dynamins or dynamin-related
proteins. 相似文献
106.
Repair of wounds usually results in restoration of organ function, even if suboptimal. However, in a minority of situations,
the healing process leads to significant scarring that hampers homeostasis and leaves the tissue compromised. This scar is
characterized by an excess of matrix deposition that remains poorly organized and weakened. While we know much of the early
stages of the repair process, the transition to wound resolution that limits scar formation is poorly understood. This is
particularly true of the inducers of scar formation. Here, we present a hypothesis that it is the matrix itself that is a
primary driver of scar, rather than being simply the result of other cellular dysregulations. 相似文献
107.
108.
Gutiérrez-López MD Gilsanz A Yáñez-Mó M Ovalle S Lafuente EM Domínguez C Monk PN González-Alvaro I Sánchez-Madrid F Cabañas C 《Cellular and molecular life sciences : CMLS》2011,68(19):3275-3292
ADAM17/TACE is a metalloproteinase responsible for the shedding of the proinflammatory cytokine TNF-α and many other cell
surface proteins involved in development, cell adhesion, migration, differentiation, and proliferation. Despite the important
biological function of ADAM17, the mechanisms of regulation of its metalloproteinase activity remain largely unknown. We report
here that the tetraspanin CD9 and ADAM17 partially co-localize on the surface of endothelial and monocytic cells. In situ
proximity ligation, co-immunoprecipitation, crosslinking, and pull-down experiments collectively demonstrate a direct association
between these molecules. Functional studies reveal that treatment with CD9-specific antibodies or neoexpression of CD9 exert
negative regulatory effects on ADAM17 sheddase activity. Conversely, CD9 silencing increased the activity of ADAM17 against
its substrates TNF-α and ICAM-1. Taken together, our results show that CD9 associates with ADAM17 and, through this interaction,
negatively regulates the sheddase activity of ADAM17. 相似文献
109.
110.