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61.
Sakata E Yamaguchi Y Miyauchi Y Iwai K Chiba T Saeki Y Matsuda N Tanaka K Kato K 《Nature structural & molecular biology》2007,14(2):167-168
Although cullin-1 neddylation is crucial for the activation of SCF ubiquitin E3 ligases, the underlying mechanisms for NEDD8-mediated activation of SCF remain unclear. Here we demonstrate by NMR and mutational studies that NEDD8 binds the ubiquitin E2 (UBC4), but not NEDD8 E2 (UBC12). Our data imply that NEDD8 forms an active platform on the SCF complex for selective recruitment of ubiquitin-charged E2s in collaboration with RBX1, and thereby upregulates the E3 activity. 相似文献
62.
Hiroyuki Sonoda Haku Iizuka Sho Ishiwata Daisuke Tsunoda Masako Abe Kenji Takagishi Hirotaka Chikuda Noriyuki Koibuchi Noriaki Shimokawa 《Journal of cellular biochemistry》2019,120(9):15007-15017
Although congenital scoliosis is defined as a genetic disease characterized by a congenital and abnormal curvature of the spinal vertebrae, our knowledge of the genetic underpinnings of the disease is insufficient. We herein show that the downregulation of the retinol-retinoic acid metabolism pathway is involved in the pathogenesis of congenital scoliosis. By analyzing DNA microarray data, we found that the expression levels of genes associated with the retinol metabolism pathway were decreased in the lumbar spine of Ishibashi rats (IS), a rat model of congenital kyphoscoliosis. The expression of Adh1 and Aldh1a2 (alcohol dehydrogenase), two enzymes that convert retinol to retinoic acid in this pathway, were decreased at both the gene and protein levels. Rarα, a receptor of retinoic acid and bone morphogenetic protein 2, which play a central role in bone formation and are located downstream of this pathway, were also downregulated. Interestingly, the serum retinol levels of IS rats were higher than those of wild-type control rats. These results indicate that the adequate conversion from retinol to retinoic acid is extremely important in the regulation of normal bone formation and it may also be a key factor for understanding the pathogenesis of congenital scoliosis. 相似文献
63.
A transgenic rat was used as a transplantation donor to simulate autologous transplantation. The sex-matched transplantation between a female transgenic and a wild-type rat can theoretically be regarded as an autologous transplantation due to the genetic agreement of these rats except for the non-protein-producing transgenes. Transgene-containing synovial cells were tracked in the joint using this autologous transplantation model. The transgenes in the donor synovial cells were detected using in situ hybridization (ISH), while mitotic activities were simultaneously examined by immunodetection of 5-bromo-2'-deoxyuridine (BrdU). A defect was generated in the knee joint capsule of a Fischer 344 (wild-type) rat. The synovium of a transgenic rat was sutured to the defect of the wild-type rat in group 1 and was allowed to free float in the joint in group 2. A large number of BrdU-labeled, transgene-containing synovial cells were detected in both groups at 3 days. The number of these cells then decreased, but they could still be identified even at 4 weeks after autologous transplantation. These results indicated that transplanted synovial cells were viable in the joint for at least 4 weeks. Furthermore, the transgenic rat was shown to be an effective animal model for distinguishing the extrinsic from the intrinsic cells in the cellular intermixed tissues in vivo. The combined method of ISH for detecting transgene-containing cells and the immunohistochemistry of BrdU for detecting proliferating cells was also shown to be effective for tracking the viability of extrinsic cells after autologous transplantation. 相似文献
64.
During Xenopus development, embryonic cells dramatically change their shape and position. Rho family small GTPases, such as RhoA, Rac, and Cdc42, play important roles in this process. These GTPases are generally activated by guanine nucleotide exchange factors (GEFs); however, the roles of RhoGEFs in Xenopus development have not yet been elucidated. We therefore searched for RhoGEF genes in our Xenopus EST database, and we identified several genes expressed during embryogenesis. Among them, we focused on one gene, designated xNET1. It is similar to mammalian NET1, a RhoA-specific GEF. An in vitro binding assay revealed that xNET1 bound to RhoA, but not to Rac or Cdc42. In addition, transient expression of xNET1 activated endogenous RhoA. These results indicated that xNET1 is a GEF for RhoA. Epitope-tagged xNET1 was localized mainly to the nucleus, and the localization was regulated by nuclear localization signals in the N-terminal region of xNET1. Overexpression of either wild-type or a mutant form of xNET1 severely inhibited gastrulation movements. We demonstrated that xNET1 was co-immunoprecipitated with the Dishevelled protein, which is an essential signaling component in the non-canonical Wnt pathway. This pathway has been shown to activate RhoA and regulate gastrulation movements. We propose that xNET1 or a similar RhoGEF may mediate Dishevelled signaling to RhoA in the Wnt pathway. 相似文献
65.
Wakahara K Kobayashi H Yagyu T Matsuzaki H Kondo T Kurita N Sekino H Inagaki K Suzuki M Kanayama N Terao T 《Journal of cellular biochemistry》2004,93(3):437-453
The net balance between urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) has been implicated in tumor cell invasion and metastasis. To elucidate the mechanism of the transforming growth factor-beta1 (TGF-beta1)-dependent up-regulation of PAI-1 expression, we investigated which signaling pathway transduced by TGF-beta1 is responsible for this effect. Here, we show (1) nontoxic concentrations of TGF-beta1 up-regulates uPA expression in HRA and SKOV-3 human ovarian cancer cells, (2) TGF-beta1 activates Smads (phosphorylation of Smad2 and nuclear translocation of Smad3) and subsequently up-regulates PAI-1 expression in HRA cells, whereas TGF-beta1 neither activates Smads nor up-regulates PAI-1 in SKOV-3 cells, (3) pharmacological Src inhibitor PP2 or antisense (AS) c-Src oligodeoxynucleotide (ODN) treatment significantly induces TGF-beta1-dependent activation of Smads, leading to PAI-1 synthesis, compared with controls, in SKOV-3 cells, (4) combination of TGF-beta1 and PP2, which activates PAI-1 expression and reduces uPA expression in SKOV-3, results in decreased invasiveness, (5) pharmacological inhibitors for mitogen-activated protein kinase (MAPK) (PD98059) and phosphoinositide-3-kinase (PI3K) (LY294002 and wortmannin) or AS-PI3K ODN transfection do not affect TGF-beta1-induced Smad signaling and up-regulation of PAI-1 expression in SKOV-3 cells pretreated with PP2, and (6) the induction of PAI-1 protein was partially inhibited by an inhibitor of Sp1-DNA binding, mithramycin, implicating, at least in part, Sp1 in the regulation of this gene by TGF-beta1. In conclusion, TGF-beta1-dependent activation of Smad2/3, leading to PAI-1 synthesis, may be negatively regulated by Src, but not its downstream targets MAPK and PI3K in SKOV-3 cells. These data also reflect the complex biological effect of uPA-PAI-1 system. 相似文献
66.
Yukiko?MATSUURAEmail author Yoshihiko?SASAMOTO Kenji?SATO Yoshiyuki?TAKAHASHI Masatsugu?SUZUKI Noriyuki?OHTAISHI 《Ecological Research》2004,19(4):397-404
The ovarian cycle and conception of sika deer were studied to reveal factors responsible for delayed conception. Concentration of progesterone in feces from 12 female Hokkaido sika deer (Cervus nippon yesoensis Heude, 1884) was measured during the mating season in 2000. The cyclic pattern of fecal progesterone synchronized with estrous symptoms, which could hence be interpreted as indicating ovarian cycle. All observed females ovulated by 14 October. However, during the early mating season, females did not permit copulation at ovulation, and the length of luteal phase following ovulation without estrus was 9.8±4.6 days (5–24days). Most females conceived at the first copulation, which were confirmed by progesterone profiles that was sustained at a high level after the copulation. This indicates the presence of a functional corpus luteum, a state of pregnancy. Thus, some females had repeated ovulation without copulation several times, creating a 3–4week variation in the timing of conception. But some females conceived very late in the mating season after the repetition of ovulation and copulation. 相似文献
67.
Naturally occurring isothiocyanates are effective chemoprotective agents against chemical carcinogenesis in experimental animals. In the present study, we clarified the molecular mechanism underlying the relationship between benzyl isothiocyanate (BITC)-induced cell cycle arrest and apoptosis. The exposure of HL-60 cells to BITC resulted in the inhibition of the G2/M progression that coincided with the apoptosis induction. We demonstrated that BITC significantly up-regulated expression of the G2/M cell cycle arrest-regulating genes including p21, GADD45, and 14-3-3sigma. Thus, these gathered data further supported that BITC has a potential to induce apoptosis selectively in the proliferating pre-cancerous cells through a cell cycle arrest-dependent mechanism. 相似文献
68.
Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis 总被引:4,自引:0,他引:4
Antifungal activity guided fractionation of the n-butanol extract from the methanol extract of the leaves of Artocarpus nobilis furnished 2',4',4-trihydroxy-3'-geranylchalcone (1), 2 ',4',4-trihydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (2), 2',4',4-trihydroxy-3'-[2-hydroxy-7-methyl-3-methylene-6-octaenyl]chalcone (3), 2',3,4,4'-tetrahydroxy-3'-geranylchalcone (4), 2',3,4,4'-tetrahydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (5). The chalcones 3 and 5 are new natural products whereas 1 and 2 are reported first time from the family Moraceae. All these compounds showed good fungicidal activity against Cladosporium cladosporioides and high radical scavenging activity towards the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical in TLC bio-autography method. 相似文献
69.
Plant-specific microtubule-associated protein SPIRAL2 is required for anisotropic growth in Arabidopsis
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Shoji T Narita NN Hayashi K Hayashi K Asada J Hamada T Sonobe S Nakajima K Hashimoto T 《Plant physiology》2004,136(4):3933-3944
In diffusely growing plant cells, cortical microtubules play an important role in regulating the direction of cell expansion. Arabidopsis (Arabidopsis thaliana) spiral2 (spr2) mutant is defective in directional cell elongation and exhibits right-handed helical growth in longitudinally expanding organs such as root, hypocotyl, stem, petiole, and petal. The growth of spr2 roots is more sensitive to microtubule-interacting drugs than is wild-type root growth. The SPR2 gene encodes a plant-specific 94-kD protein containing HEAT-repeat motifs that are implicated in protein-protein interaction. When expressed constitutively, SPR2-green fluorescent protein fusion protein complemented the spr2 mutant phenotype and was localized to cortical microtubules as well as other mitotic microtubule arrays in transgenic plants. Recombinant SPR2 protein directly bound to taxol-stabilized microtubules in vitro. Furthermore, SPR2-specific antibody and mass spectrometry identified a tobacco (Nicotiana tabacum) SPR2 homolog in highly purified microtubule-associated protein fractions from tobacco BY-2 cell cultures. These results suggest that SPR2 is a novel microtubule-associated protein and is required for proper microtubule function involved in anisotropic growth. 相似文献
70.
Esaki H Noda K Otsuki N Kojima A Asai T Tamura Y Takahashi T 《Journal of microbiological methods》2004,58(1):131-134
A total of 63 isolates were screened for the gyrA mutation (87Asp-Tyr) in Salmonella enterica serovars using real time PCR. All of the isolates were successfully identified as resistant or susceptible, consistent with the MIC result of the agar dilution method and gyrA sequencing. 相似文献