共查询到20条相似文献,搜索用时 15 毫秒
1.
Jae Eun Park Byoung Chul Park Hyun-A Kim Mina Song Sung Goo Park Do Hee Lee Hyeoung-Joon Kim Hyung-Kyoon Choi Jong-Tae Kim Sayeon Cho 《Cellular and molecular life sciences : CMLS》2010,67(15):2619-2629
Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1. 相似文献
2.
Isabel F. Fernández Luis G. Pérez-Rivas Sandra Blanco Adrián A. Castillo-Dominguez José Lozano Pedro A. Lazo 《Cellular and molecular life sciences : CMLS》2012,69(22):3881-3893
The spatial and temporal regulation of intracellular signaling is determined by the spatial and temporal organization of complexes assembled on scaffold proteins, which can be modulated by their interactions with additional proteins as well as subcellular localization. The scaffold KSR1 protein interacts with MAPK forming a complex that conveys a differential signaling in response to growth factors. The aim of this work is to determine the unknown mechanism by which VRK2A downregulates MAPK signaling. We have characterized the multiprotein complex formed by KSR1 and the Ser-Thr kinase VRK2A. VRK2A is a protein bound to the endoplasmic reticulum (ER) and retains a fraction of KSR1 complexes on the surface of this organelle. Both proteins, VRK2A and KSR1, directly interact by their respective C-terminal regions. In addition, MEK1 is also incorporated in the basal complex. MEK1 independently interacts with the CA5 region of KSR1 and with the N-terminus of VRK2A. Thus, VRK2A can form a high molecular size (600–1,000?kDa) stable complex with both MEK1 and KSR1. Knockdown of VRK2A resulted in disassembly of these high molecular size complexes. Overexpression of VRK2A increased the amount of KSR1 in the particulate fraction and prevented the incorporation of ERK1/2 into the complex after stimulation with EGF. Neither VRK2A nor KSR1 interact with the VHR, MKP1, MKP2, or MKP3 phosphatases. The KSR1 complex assembled and retained by VRK2A in the ER can have a modulatory effect on the signal mediated by MAPK, thus locally affecting the magnitude of its responses, and can explain differential responses depending on cell type. 相似文献
3.
Parkinson’s disease (PD) is characterized by the death of dopaminergic neurons and the presence of Lewy bodies in the substantia
nigra pars compacta. The mechanisms involved in the death of neurons as well as the role of Lewy bodies in the pathogenesis
of the disease are still unclear. Lewy bodies are made of aggregated proteins, in which α-synuclein represents their major
component. α-Synuclein interacts with synphilin-1, a protein that is also present in Lewy bodies. When expressed in cells,
synphilin-1 forms inclusions together with α-synuclein that resemble Lewy bodies. Synphilin-1 is ubiquitylated by various
E3 ubiquitin-ligases, such as SIAH, parkin and dorfin. Ubiquitylation of synphilin-1 by SIAH is essential for its aggregation
into inclusions. We recently identified a new synphilin-1 isoform, synphilin-1A, that is toxic to neurons, aggregation-prone
and accumulates in detergent-insoluble fractions of brains from α-synucleinopathy patients. Synphilin-1A inclusions recruit
both α-synuclein and synphilin-1. Aggregation of synphilin-1 and synphilin-1A seems to be protective to cells. We now discuss
several aspects of the neurobiology and pathology of synphilin-1 isoforms, focusing on possible implications for PD.
Received 26 July 2007; received after revision 19 September 2007; accepted 15 October 2007 相似文献
4.
Joongkyu Park Woo-Joo Song Kwang Chul Chung 《Cellular and molecular life sciences : CMLS》2009,66(20):3235-3240
Down syndrome (DS) is associated with a variety of symptoms, such as incapacitating mental retardation and neurodegeneration
(i.e., Alzheimer’s disease), that prevent patients from leading fully independent lives. These phenotypes are a direct consequence
of the overexpression of chromosome 21 genes, which are present in duplicate due to non-disjunction of chromosome 21. Accumulating
data suggest that the chromosome 21 gene product, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (Dyrk1A),
participates in the pathogenic mechanisms underlying the mental and other physical symptoms of DS. In this review, we summarize
the evidence supporting a role for Dyrk1A in DS, especially DS pathogenesis. Recently, several natural and synthetic compounds
have been identified as Dyrk1A inhibitors. Understanding the function and regulation of Dyrk1A may lead to the development
of novel therapeutic agents aimed at treating DS. 相似文献
5.
J P Caruelle J C Baehr P Cassier 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1979,288(14):1107-1110
Corpora allata of Locusta migratoria 5th stage larvae synthesize J.H.1, J.H.2 and J.H.3 in vitro. The C.A. of insects of different ages exbit different rates of J.H. synthesis. J.H.1 and J.H.2 synthesis is less than 1 ng/48 h/gland. During the same time the J.H.3 production may be as much as 25.6 ng/gland. J.H. synthetic activity is the same between right and left C.A. The release of J.H. from the C.A. occurs immediately following synthesis. These results are compared with in vivo haemolymphatic J.H. levels. 相似文献
6.
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
7.
Gabriele Eden Marco Archinti Ralitsa Arnaudova Giuseppina Andreotti Andrea Motta Federico Furlan Valentina Citro Maria Vittoria Cubellis Bernard Degryse 《Cellular and molecular life sciences : CMLS》2018,75(10):1889-1907
The urokinase receptor (uPAR) stimulates cell proliferation by forming a macromolecular complex with αvβ3 integrin and the epidermal growth factor receptor (EGFR, ErbB1 or HER1) that we name the uPAR proliferasome. uPAR transactivates EGFR, which in turn mediates uPAR-initiated mitogenic signal to the cell. EGFR activation and EGFR-dependent cell growth are blocked in the absence of uPAR expression or when uPAR activity is inhibited by antibodies against either uPAR or EGFR. The mitogenic sequence of uPAR corresponds to the D2A motif present in domain 2. NMR analysis revealed that D2A synthetic peptide has a particular three-dimensional structure, which is atypical for short peptides. D2A peptide is as effective as EGF in promoting EGFR phosphorylation and cell proliferation that were inhibited by AG1478, a specific inhibitor of the tyrosine kinase activity of EGFR. Both D2A and EGF failed to induce proliferation of NR6-EGFR-K721A cells expressing a kinase-defective mutant of EGFR. Moreover, D2A peptide and EGF phosphorylate ERK demonstrating the involvement of the MAP kinase signalling pathway. Altogether, this study reveals the importance of sequence D2A of uPAR, and the interdependence of uPAR and EGFR. 相似文献
8.
Vonk WI de Bie P Wichers CG van den Berghe PV van der Plaats R Berger R Wijmenga C Klomp LW van de Sluis B 《Cellular and molecular life sciences : CMLS》2012,69(1):149-163
Menkes disease (MD) is an X-linked recessive disorder characterized by copper deficiency resulting in a diminished function
of copper-dependent enzymes. Most MD patients die in early childhood, although mild forms of MD have also been described.
A diversity of mutations in the gene encoding of the Golgi-resident copper-transporting P1B-type ATPase ATP7A underlies MD. To elucidate the molecular consequences of the ATP7A mutations, various mutations in ATP7A associated with distinct phenotypes of MD (L873R, C1000R, N1304S, and A1362D) were analyzed in detail. All mutants studied
displayed changes in protein expression and intracellular localization parallel to a dramatic decline in their copper-transporting
capacity compared to ATP7A the wild-type. We restored these observed defects in ATP7A mutant proteins by culturing the cells
at 30°C, which improves the quality of protein folding, similar to that which as has recently has been demonstrated for misfolded
ATP7B, a copper transporter homologous to ATP7A. Further, the effect of the canine copper toxicosis protein COMMD1 on ATP7A
function was examined as COMMD1 has been shown to regulate the proteolysis of ATP7B proteins. Interestingly, in addition to
adjusted growth temperature, binding of COMMD1 partially restored the expression, subcellular localization, and copper-exporting
activities of the ATP7A mutants. However, no effect of pharmacological chaperones was observed. Together, the presented data
might provide a new direction for developing therapies to improve the residual exporting activity of unstable ATP7A mutant
proteins, and suggests a potential role for COMMD1 in this process. 相似文献
9.
10.
Summary From sting extracts ofApis dorsata andA. florea, a substance was isolated which is active in alarm behaviour of both of these species but not ofA. mellifera andA. cerana. The active substance was identified as 2-decen-1-yl-acetate. 相似文献
11.
Caspar Grond-Ginsbach Rastislav Pjontek Suna Su Aksay Alexander Hyhlik-Dürr Dittmar Böckler Marie-Luise Gross-Weissmann 《Cellular and molecular life sciences : CMLS》2010,67(11):1799-1815
Arterial dissection (AD) is defined as the longitudinal splitting up of the arterial wall caused by intramural bleeding. It
can occur as a spontaneous event in all large and medium sized arteries. The histological hallmark of AD is medial degeneration.
Histological investigations, gene expression profiling and proteome studies of affected arteries reveal disturbances in many
different biological processes including inflammation, proteolytic activity, cell proliferation, apoptosis and smooth muscle
cell (SMC) contractile function. Medial degeneration can be caused by various rare dominant Mendelian disorders. Genetic linkage
analysis lead to the identification of mutations in different disease-causing genes involved in the biosynthesis of the extracellular
matrix (FBN1, COL3A1), in transforming growth factor (TGF) beta signaling (FBN1, TGFBR1, TGFBR2) and in the SMC contractile
system (ACTA2, MYH11). Genome wide association studies suggest that the CDKN2A/CDKN2B locus plays a role in the etiology AD
and other arterial diseases. 相似文献
12.
Marta Bolos Carlos Spuch Lara Ordoñez-Gutierrez Francisco Wandosell Isidro Ferrer Eva Carro 《Cellular and molecular life sciences : CMLS》2013,70(15):2787-2797
β-amyloid (Aβ) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer’s disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of Aβ on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that Aβ regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric Aβ increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These Aβ-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished Aβ-induced neuronal proliferation. Taken together, our results support a role of Aβ in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer’s disease. 相似文献
13.
P Walter 《Experientia》1991,47(2):178-181
Some recent evidence on the benefits and hazards of elevated dosages of vitamins is summarized. Special emphasis is given on the safety of vitamins A, D, K1 and B6. Furthermore, the possibly beneficial effects of vitamins for athletic performance as well as the preventive potential of antioxidative vitamins and of carotenoids against cancer are discussed. 相似文献
14.
C Bottex D Robert R Fontanges 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1977,284(19):1943-1946
An intranasal immunization with a A/PR8/34-isolated NA, protected mice as well as the whole virus and A/Hong Kong/1/68 virus against a subsequent infection with mice-adaptated A/PR8/34 strain. 相似文献
15.
Sarno S Mazzorana M Traynor R Ruzzene M Cozza G Pagano MA Meggio F Zagotto G Battistutta R Pinna LA 《Cellular and molecular life sciences : CMLS》2012,69(3):449-460
8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of
protein kinase CK2 (Ki = 0.22 μM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter
as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as
“denitro NBC”, dNBC), the inhibitory power toward CK2 is almost entirely lost (IC50 > 30 μM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases
that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC50 values with NBC and dNBC are 15 and 0.60 μM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent
inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural
features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit
of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68
and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved
water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to
the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A
by dNBC. 相似文献
16.
17.
J. R. Aldrich J. P. Kochansky J. D. Sexton 《Cellular and molecular life sciences : CMLS》1985,41(3):420-422
Summary Workers and queens of the eastern yellowjacket,Vespula maculifrons, are attracted to the artificial long-range attractant pheromone of the predaceous pentatomid,Podisus maculiventris. A 11 mixture of linalool or -terpineol and (E)-2-hexenal is as attractive toV. maculifrons workers as the pheromone.We thank A.S. Menke of the Systematic Entomology Laboratory, USDA, for identifying the yellowjackets. Mention of a company name does not imply endorsement by the US Department of Agriculture. 相似文献
18.
What’s new in the renin-angiotensin system? 总被引:5,自引:0,他引:5
Warner FJ Smith AI Hooper NM Turner AJ 《Cellular and molecular life sciences : CMLS》2004,61(21):2704-2713
Angiotensin-converting enzyme-2 (ACE2) is the first human homologue of ACE to be described. ACE2 is a type I integral membrane protein which functions as a carboxypeptidase, cleaving a single hydrophobic/basic residue from the C-terminus of its substrates. ACE2 efficiently hydrolyses the potent vasoconstrictor angiotensin II to angiotensin (1-7). It is a consequence of this action that ACE2 participates in the renin-angiotensin system. However, ACE2 also hydrolyses dynorphin A (1-13), apelin-13 and des-Arg(9) bradykinin. The role of ACE2 in these peptide systems has yet to be revealed. A physiological role for ACE2 has been implicated in hypertension, cardiac function, heart function and diabetes, and as a receptor of the severe acute respiratory syndrome coronavirus. This paper reviews the biochemistry of ACE2 and discusses key findings such as the elucidation of crystal structures for ACE2 and testicular ACE and the development of ACE2 inhibitors that have now provided a basis for future research on this enzyme. 相似文献
19.
Verónica Parrillas Laura Martínez-Muñoz Borja L. Holgado Amit Kumar Graciela Cascio Pilar Lucas José Miguel Rodríguez-Frade Marcos Malumbres Ana C. Carrera Karel HM van Wely Mario Mellado 《Cellular and molecular life sciences : CMLS》2013,70(3):545-558
Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma. 相似文献
20.
Profiling of the secreted proteins during 3T3-L1 adipocyte differentiation leads to the identification of novel adipokines 总被引:3,自引:0,他引:3
Wang P Mariman E Keijer J Bouwman F Noben JP Robben J Renes J 《Cellular and molecular life sciences : CMLS》2004,61(18):2405-2417
Adipose tissue is an endocrine organ capable of secreting a number of adipokines with a role in the regulation of
adipose tissue and whole-body metabolism. We used two-dimensional gel electrophoresis combined with mass spectrometry to
profile the secreted proteins from (pre)adipocytes. The culture medium of 3T3-L1 cells during adipocyte differentiation
was screened, and 41 proteins that responded to blocking of secretion by 20°C treatment and/or brefeldin A treatment
were identified. Prohibitin, stress-70 protein, and adhesion-regulating molecule 1 are reported for the first time as
secreted proteins. In addition, procollagen C-proteinase enhancer protein, galectin-1, cyclophilin A and C, and SF20/IL-25
are newly identified as adipocyte secreted factors. Secretion profiles indicated a dynamic environment including an
actively remodeling extracellular matrix and several factors involved in growth regulation.Received 15 June 2004; received after revision 26 July 2004; accepted 2 August 2004 相似文献