共查询到20条相似文献,搜索用时 15 毫秒
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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
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Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential 总被引:1,自引:0,他引:1
Salminen A Lehtonen M Suuronen T Kaarniranta K Huuskonen J 《Cellular and molecular life sciences : CMLS》2008,65(19):2979-2999
Traditional medicine has been a fertile source for revealing novel lead molecules for modern drug discovery. In plants, terpenoids
represent a chemical defense against environmental stress and provide a repair mechanism for wounds and injuries. Interestingly,
effective ingredients in several plant-derived medicinal extracts are also terpenoid compounds of monoterpenoid, sesquiterpenoid,
diterpenoid, triterpenoid and carotenoid groups. Inflammatory diseases and cancer are typical therapeutic indications of traditional
medicines. Thus folk medicine supports the studies which have demonstrated that plant-derived terpenoid ingredients can suppress
nuclear factor-κB (NF-κB) signaling, the major regulator in the pathogenesis of inflammatory diseases and cancer.We review
the extensive literature on the different types of terpenoid molecules, totalling 43, which have been verified both inhibiting
the NF-κB signaling and suppressing the process of inflammation and cancer. It seems that during evolution, plants have established
a terpene-based host defense which also represents a cornucopia of effective therapeutic compounds for common human diseases.
Received 11 March 2008; received after revision 28 April 2008; accepted 29 April 2008 相似文献
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Salminen A Ojala J Huuskonen J Kauppinen A Suuronen T Kaarniranta K 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1049-1058
Research on aging in model organisms has revealed different molecular mechanisms involved in the regulation of the lifespan.
Studies on Saccharomyces cerevisiae have highlighted the role of the Sir2 family of genes, human Sirtuin homologs, as the longevity factors. In Caenorhabditis elegans, the daf-16 gene, a mammalian homolog of FoxO genes, was shown to function as a longevity gene. A wide array of studies has
provided evidence for a role of the activation of innate immunity during aging process in mammals. This process has been called
inflamm-aging. The master regulator of innate immunity is the NF-κB system. In this review, we focus on the several interactions
of aging-associated signaling cascades regulated either by Sirtuins and FoxOs or NF-κB signaling pathways. We provide evidence
that signaling via the longevity factors of FoxOs and SIRT1 can inhibit NF-κB signaling and simultaneously protect against inflamm-aging process.
Received 4 October 2007; received after revision 7 November 2007; accepted 9 November 2007 相似文献
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Sami Reijonen Jyrki P. Kukkonen Alise Hyrskyluoto Jenny Kivinen Minna Kairisalo Nobuyuki Takei Dan Lindholm Laura Korhonen 《Cellular and molecular life sciences : CMLS》2010,67(11):1929-1941
Accumulation of abnormal proteins and endoplasmic reticulum stress accompany neurodegenerative diseases including Huntington’s
disease. We show that the expression of mutant huntingtin proteins with extended polyglutamine repeats differentially affected
endoplasmic reticulum signaling cascades linked to the inositol-requiring enzyme-1 (IRE1) pathway. Thus, the p38 and c-Jun
N-terminal kinase pathways were activated, while the levels of the nuclear factor-κB-p65 (NF-κB-p65) protein decreased. Downregulation
of NF-κB signaling was linked to decreased antioxidant levels, increased oxidative stress, and enhanced cell death. Concomitantly,
calpain was activated, and treatment with calpain inhibitors restored NF-κB-p65 levels and increased cell viability. The calpain
regulator, calpastatin, was low in cells expressing mutant huntingtin, and overexpression of calpastatin counteracted the
deleterious effects caused by N-terminal mutant huntingtin proteins. These results show that calpastatin and an altered NF-κB-p65
signaling are crucial factors involved in oxidative stress and cell death mediated by mutant huntingtin proteins. 相似文献
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Silberman DM Zorrilla-Zubilete M Cremaschi GA Genaro AM 《Cellular and molecular life sciences : CMLS》2005,62(15):1744-1754
Chronic stress has been associated with impaired immune function. In this work we studied the effect of chronic mild stress (CMS) exposure on the early intracellular pathways involved in T cells after stimulation with mitogen. We found that mitogen stimulation of T lymphocytes from CMS-exposed mice resulted in a reduction of the intracellular [Ca2+] rise, an impairment of growth-promoting protein kinase C (PKC) activation, a lower NF-κB activation and an increase in the inhibitory cAMP-protein kinase A (PKA) pathway activity with respect to those found in control lymphocytes. However, T cell activation with the direct PKC activator phorbol 12-myristate 13-acetate plus calcium ionophore led to a similar proliferative response in both CMS and control lymphocytes, indicating that signals downstream of PKC would not be affected by stress. In summary, our results show that chronic stress induced an alteration in T cell early transduction signals that result in an impairment of the proliferative response.Received 11 February 2005; received after revision 20 May 2005; accepted 6 June 2005 相似文献
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Pascal P. H. Hommelberg Jogchum Plat Lauren M. Sparks Annemie M. W. J. Schols Anon L. M. van Essen Marco C. J. M. Kelders Denis van Beurden Ronald P. Mensink Ramon C. J. Langen 《Cellular and molecular life sciences : CMLS》2011,68(7):1215-1225
Palmitate activates the NF-κB pathway, and induces accumulation of lipid metabolites and insulin resistance in skeletal muscle
cells. Little information is available whether and how these processes are causally related. Therefore, the objectives were
to investigate whether intra-cellular lipid metabolites are involved in FA-induced NF-κB activation and/or insulin resistance
in skeletal muscle and to investigate whether FA-induced insulin resistance and NF-κB activation are causally related. Inhibiting
DGAT or CPT-1 by using, respectively, amidepsine or etomoxir increased DAG accumulation and sensitized myotubes to palmitate-induced
insulin resistance. While co-incubation of palmitate with etomoxir increased NF-κB transactivation, co-incubation with amidepsine
did not, indicating that DAG accumulation is associated with insulin resistance but not with NF-κB activation. Furthermore,
pharmacological or genetic inhibition of the NF-κB pathway could not prevent palmitate-induced insulin resistance. In conclusion,
we have demonstrated that activation of the NF-κB pathway is not required for palmitate-induced insulin resistance in skeletal
muscle cells. 相似文献
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Members of the tumor necrosis factor receptor (TNFR) family regulate the activation, differentiation, and function of many cell types, including cells of the immune system. TNFR-associated factors (TRAFs) function as adapter molecules controlling signaling pathways triggered by TNFR family members, such as activation of nuclear factor B (NF-B). Despite intensive research, the function of TRAF4 in signaling pathways triggered by TNFR-related proteins remains enigmatic. Intriguingly, our functional studies indicated that TRAF4 augments NF-B activation triggered by glucocorticoid-induced TNFR (GITR), a receptor expressed on T cells, B cells, and macrophages. Further analyses revealed that TRAF4-mediated NF-B activation downstream of GITR depends on a previously mapped TRAF-binding site in the cytoplasmic domain of the receptor and is inhibited by the cytoplasmic protein A20. GITR is thought to inhibit the suppressive function of regulatory T cells (Treg cells) and to promote activation of T cells. Taken together, our studies provide the first indications that TRAF4 elaborates GITR signaling and suggest that TRAF4 can modulate the suppressive functions of Treg cells.Received 20 September 2004; received after revision 8 October 2004; accepted 18 October 2004 相似文献
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Dong Gao Ruipeng Wang Bingfeng Li Yongkang Yang Zhonghe Zhai Dan-Ying Chen 《Cellular and molecular life sciences : CMLS》2009,66(15):2573-2584
Toll-like receptors (TLRs) act as sensors of microbial components and elicit innate immune responses. All TLR signaling pathways
activate the nuclear factor-kappaB (NF-κB), which controls the expression of inflammatory cytokine genes. Transforming growth
factor-β-activated kinase 1 (TAK1) is a serine/threonine protein kinase that is critically involved in the activation of NF-κB
by tumor necrosis factor (TNFα), interleukin-1β (IL-1β) and TLR ligands. In this study, we identified a novel protein, WD40
domain repeat protein 34 (WDR34) as a TAK1-interacting protein in yeast two-hybrid screens. WDR34 interacted with TAK1, TAK1-binding
protein 2 (TAB2), TAK1-binding protein 3 (TAB3) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in overexpression
and under physiological conditions. Overexpression of WDR34 inhibited IL-1β-, polyI:C- and lipopolysaccharide (LPS)-induced
but not TNFα-induced NF-κB activation, whereas knockdown of WDR34 by a RNA-interference construct potentiated NF-κB activation
by these ligands. Our findings suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-κB activation
pathway.
D. Gao and R. Wang contributed equally to this work. 相似文献