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101.
Important to the function of calpains is temporal and spatial regulation of their proteolytic activity. Here, we demonstrate
that cytoplasm-resident calpain 2 cleaves human nuclear topoisomerase I (hTOP1) via Ca2+-activated proteolysis and nucleoplasmic shuttling of proteases. This proteolysis of hTOP1 was induced by either ionomycin-caused
Ca2+ influx or addition of Ca2+ in cellular extracts. Ca2+ failed to induce hTOP1 proteolysis in calpain 2-knockdown cells. Moreover, calpain 2 cleaved hTOP1 in vitro. Furthermore,
calpain 2 entered the nucleus upon Ca2+ influx, and calpastatin interfered with this process. Calpain 2 cleavage sites were mapped at K158 and K183 of hTOP1. Calpain 2-truncated hTOP1 exhibited greater relaxation activity but remained able to interact with nucleolin and
to form cleavable complexes. Interestingly, calpain 2 appears to be involved in ionomycin-induced protection from camptothecin-induced
cytotoxicity. Thus, our data suggest that nucleocytoplasmic shuttling may serve as a novel type of regulation for calpain
2-mediated nuclear proteolysis. 相似文献
102.
The myogenic transcriptional network 总被引:2,自引:0,他引:2
103.
Khan ZU Martín-Montañez E Baxter MG 《Cellular and molecular life sciences : CMLS》2011,68(10):1737-1754
Visual perception and memory are the most important components of vision processing in the brain. It was thought that the
perceptual aspect of a visual stimulus occurs in visual cortical areas and that this serves as the substrate for the formation
of visual memory in a distinct part of the brain called the medial temporal lobe. However, current evidence indicates that
there is no functional separation of areas. Entire visual cortical pathways and connecting medial temporal lobe are important
for both perception and visual memory. Though some aspects of this view are debated, evidence from both sides will be explored
here. In this review, we will discuss the anatomical and functional architecture of the entire system and the implications
of these structures in visual perception and memory. 相似文献
104.
Naturally occurring antimicrobial peptides (AMPs) present several drawbacks that strongly limit their development into therapeutically
valuable antibiotics. These include susceptibility to protease degradation and high costs of manufacture. To overcome these
problems, researchers have tried to develop mimics or peptidomimetics endowed with better properties, while retaining the
basic features of membrane-active natural AMPs such as cationic charge and amphipathic design. Protein epitope mimetics, multimeric
(dendrimeric) peptides, oligoacyllysines, ceragenins, synthetic lipidated peptides, peptoids and other foldamers are some
of the routes explored so far. The synthetic approach has led to compounds that have already entered clinical evaluation for
the treatment of specific conditions, such as Staphylococcus (MRSA) infections. Should these trials be successful, an important proof-of-concept would be established, showing that synthetic
oligomers rather than naturally occurring molecules could bring peptide-based antibiotics to clinical practice and the drug
market for local and systemic treatment of medical conditions associated with multi-drug resistant pathogens. 相似文献
105.
Good MF 《Cellular and molecular life sciences : CMLS》2011,68(7):1105-1113
Malaria presents a challenge to world health that to date has been beyond the abilities of researchers to conquer. This critique
presents some of the strategies employed by the parasite to overcome immunity and the immunological challenges that we face
to develop vaccines. A conclusion is that a vaccine must identify novel antigens or epitopes that are not normally immunogenic
and which are therefore not under immune pressure and most likely to be conserved between different strains. Such antigens
are most likely to be targets of cellular immunity. The case for a whole parasite blood stage vaccine is presented based on
these premises. 相似文献
106.
Marsango S Bonaccorsi di Patti MC Barra D Miele R 《Cellular and molecular life sciences : CMLS》2011,68(17):2919-2929
Prokineticins are proteins that regulate diverse biological processes including gastrointestinal motility, angiogenesis, circadian
rhythm, and innate immune response. Prokineticins bind two closed related G-protein coupled receptors (GPCRs), PKR1 and PKR2.
In general, these receptors act as molecular switches to relay activation to heterotrimeric G-proteins and a growing body
of evidence points to the fact that GPCRs exist as homo- or heterodimers. We show here by Western-blot analysis that PKR2
has a dimeric structure in neutrophils. By heterologous expression of PKR2 in Saccharomyces cerevisiae, we examined the mechanisms of intermolecular interaction of PKR2 dimerization. The potential involvement of three types
of mechanisms was investigated: coiled-coil, disulfide bridges, and hydrophobic interactions between transmembrane domains.
Characterization of differently deleted or site-directed PKR2 mutants suggests that dimerization proceeds through interactions
between transmembrane domains. We demonstrate that co-expressing binding-deficient and signaling-deficient forms of PKR2 can
re-establish receptor functionality, possibly through a domain-swapping mechanism. 相似文献
107.
Lubka-Pathak M Shah AA Gallozzi M Müller M Zimmermann U Löwenheim H Pfister M Knipper M Blin N Schimmang T 《Cellular and molecular life sciences : CMLS》2011,68(16):2739-2749
Introduction
Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals.Results
Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots.Conclusions
We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis. 相似文献108.
Effectiveness of immune surveillance of intracellular viruses and bacteria depends upon a functioning antigen presentation
pathway that allows infected cells to reveal the presence of an intracellular pathogen. The antigen presentation pathway uses
virtually all endogenous polypeptides as a source to produce antigenic peptides that are eventually chaperoned to the cell
surface by MHC class I molecules. Intriguingly, MHC I molecules present peptides encoded not only in the primary open reading
frames but also those encoded in alternate reading frames. Here, we review recent studies on the generation of cryptic pMHC
I. We focus on the immunological significance of cryptic pMHC I, and the novel translational mechanisms that allow production
of these antigenic peptides from unconventional sources. 相似文献
109.
Lopez-Castejón G Baroja-Mazo A Pelegrín P 《Cellular and molecular life sciences : CMLS》2011,68(18):3095-3107
Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage
polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to
the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes
are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified
as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with
PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the
resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study
reveals an additional level of plasticity modulating the resolution of inflammation. 相似文献
110.
MicroRNAs (miRNAs) are short ~21-nt non-coding RNA molecules that have been shown to regulate a number of biological processes.
Previous reports have shown that overexpression of miR-128 in glioma cells inhibited cell proliferation. Literature also suggests
that miR-128 negatively regulates prostate cancer cell invasion. Here, we show that overexpression of hsa-miR-128, a brain-enriched
microRNA, induces apoptosis in HEK293T cells as elucidated by apoptosis assay, cell cycle changes, loss of mitochondrial membrane
potential and multicaspase assay. By in silico analysis, we identified a putative target site within the 3′ untranslated region
(UTR) of Bax, a proapoptotic member of the apoptosis pathway. We found that ectopic expression of hsa-miR-128 suppressed a
luciferase reporter containing the Bax-3′ UTR and reduced the levels of Bax in HEK293T cells. Taken together, our study demonstrates
that overexpression of hsa-miR-128 not only induces apoptosis in HEK293T cells but also is an endogenous regulator of Bax
protein. 相似文献