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排序方式: 共有644条查询结果,搜索用时 15 毫秒
161.
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
162.
H. J. Kim M. Y. Kim J. S. Hwang H. J. Kim J. H. Lee K. C. Chang J. -H. Kim C. W. Han J.-H. Kim H. G. Seo 《Cellular and molecular life sciences : CMLS》2010,67(12):2119-2130
Activation of peroxisome proliferator-activated receptor (PPAR) δ by GW501516, a specific PPARδ ligand, significantly inhibited interleukin (IL)-1β-induced proliferation and migration of vascular smooth muscle cells (VSMCs). This effect of GW501516 was dependent on transforming growth factor-β, and was mediated through the up-regulation of IL-1 receptor antagonist. The inhibitory effect of GW501516 on VSMC proliferation was associated with cell cycle arrest at the G1 to S phase transition, which was accompanied by the induction of p21 and p53 along with decreased cyclin-dependent kinase 4 expression. Inhibition of cell migration by GW501516 was associated with the down-regulation of matrix metalloproteinase (MMP)-2 and MMP-9 in IL-1β-treated VSMCs. Inhibition of extracellular signal-regulated kinase significantly reduced the GW501516-mediated inhibition of IL-1β-stimulated VSMC proliferation. These results suggest that PPARδ plays an important role in the pathophysiology of diseases associated with the proliferation and migration of VSMCs. 相似文献
163.
Dorota Smolarek Claude Hattab Gholamreza Hassanzadeh-Ghassabeh Sylvie Cochet Carlos Guti��rrez Alexandre G. de Brevern Rachanee Udomsangpetch Julien Picot Magdalena Grodecka Kazimiera Wasniowska Serge Muyldermans Yves Colin Caroline Le Van Kim Marcin Czerwinski Olivier Bertrand 《Cellular and molecular life sciences : CMLS》2010,67(19):3371-3387
Fy blood group antigens are carried by the Duffy antigen receptor for chemokines (DARC), a red cells receptor for Plasmodium vivax broadly implicated in human health and diseases. Recombinant VHHs, or nanobodies, the smallest intact antigen binding fragment derivative from the heavy chain-only antibodies present in camelids, were prepared from a dromedary immunized against DARC N-terminal extracellular domain and selected for DARC binding. A described VHH, CA52, does recognize native DARC on cells. It inhibits P. vivax invasion of erythrocytes and displaces interleukin-8 bound to DARC. The targeted epitope overlaps the well-defined DARC Fy6 epitope. K D of CA52?CDARC equilibrium is sub-nanomolar, hence ideal to develop diagnostic or therapeutic compounds. Immunocapture by immobilized CA52 yielded highly purified DARC from engineered K562 cells. This first report on a VHH with specificity for a red blood cell protein exemplifies VHHs?? potentialities to target, to purify, and to modulate the function of cellular markers. 相似文献
164.
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166.
Krishnan KJ Reeve AK Samuels DC Chinnery PF Blackwood JK Taylor RW Wanrooij S Spelbrink JN Lightowlers RN Turnbull DM 《Nature genetics》2008,40(3):275-279
Mitochondrial DNA (mtDNA) deletions are a primary cause of mitochondrial disease and are likely to have a central role in the aging of postmitotic tissues. Understanding the mechanism of the formation and subsequent clonal expansion of these mtDNA deletions is an essential first step in trying to prevent their occurrence. We review the previous literature and recent results from our own laboratories, and conclude that mtDNA deletions are most likely to occur during repair of damaged mtDNA rather than during replication. This conclusion has important implications for prevention of mtDNA disease and, potentially, for our understanding of the aging process. 相似文献
167.
Gupta GP Nguyen DX Chiang AC Bos PD Kim JY Nadal C Gomis RR Manova-Todorova K Massagué J 《Nature》2007,446(7137):765-770
Metastasis entails numerous biological functions that collectively enable cancerous cells from a primary site to disseminate and overtake distant organs. Using genetic and pharmacological approaches, we show that the epidermal growth factor receptor ligand epiregulin, the cyclooxygenase COX2, and the matrix metalloproteinases 1 and 2, when expressed in human breast cancer cells, collectively facilitate the assembly of new tumour blood vessels, the release of tumour cells into the circulation, and the breaching of lung capillaries by circulating tumour cells to seed pulmonary metastasis. These findings reveal how aggressive primary tumorigenic functions can be mechanistically coupled to greater lung metastatic potential, and how such biological activities may be therapeutically targeted with specific drug combinations. 相似文献
168.
Wang K Diskin SJ Zhang H Attiyeh EF Winter C Hou C Schnepp RW Diamond M Bosse K Mayes PA Glessner J Kim C Frackelton E Garris M Wang Q Glaberson W Chiavacci R Nguyen L Jagannathan J Saeki N Sasaki H Grant SF Iolascon A Mosse YP Cole KA Li H Devoto M McGrady PW London WB Capasso M Rahman N Hakonarson H Maris JM 《Nature》2011,469(7329):216-220
169.
Scheerer P Park JH Hildebrand PW Kim YJ Krauss N Choe HW Hofmann KP Ernst OP 《Nature》2008,455(7212):497-502
Opsin, the ligand-free form of the G-protein-coupled receptor rhodopsin, at low pH adopts a conformationally distinct, active G-protein-binding state known as Ops*. A synthetic peptide derived from the main binding site of the heterotrimeric G protein-the carboxy terminus of the alpha-subunit (GalphaCT)-stabilizes Ops*. Here we present the 3.2 A crystal structure of the bovine Ops*-GalphaCT peptide complex. GalphaCT binds to a site in opsin that is opened by an outward tilt of transmembrane helix (TM) 6, a pairing of TM5 and TM6, and a restructured TM7-helix 8 kink. Contacts along the inner surface of TM5 and TM6 induce an alpha-helical conformation in GalphaCT with a C-terminal reverse turn. Main-chain carbonyl groups in the reverse turn constitute the centre of a hydrogen-bonded network, which links the two receptor regions containing the conserved E(D)RY and NPxxY(x)(5,6)F motifs. On the basis of the Ops*-GalphaCT structure and known conformational changes in Galpha, we discuss signal transfer from the receptor to the G protein nucleotide-binding site. 相似文献
170.