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101.
Matsushita N Kitao H Ishiai M Nagashima N Hirano S Okawa K Ohta T Yu DS McHugh PJ Hickson ID Venkitaraman AR Kurumizaka H Takata M 《Molecular cell》2005,19(6):841-847
In DNA damage responses, the Fanconi anemia (FA) protein, FancD2, is targeted to chromatin and forms nuclear foci following its monoubiquitination, a process likely catalyzed by the FA core complex. Here, we show that a chicken FancD2-ubiquitin fusion protein, carrying a Lys-Arg substitution removing the natural monoubiquitination site (D2KR-Ub), could reverse cisplatin hypersensitivity and localize to chromatin in FANCD2-deficient DT40 cells. Importantly, the chromatin targeting was dependent on three core complex components as well as the hydrophobic surface of ubiquitin that may direct protein-protein interactions. Furthermore, a constitutively chromatin bound fusion of D2KR-histone H2B could complement cisplatin sensitivity in FANCD2- but not FANCC-, FANCG-, or FANCL-deficient cells. Thus these core complex components have an additional function in the DNA repair, which is independent of the monoubiquitination and chromatin targeting of FancD2. These results define functional consequences of FancD2 monoubiquitination and reveal previously hidden functions for the FA protein core complex. 相似文献
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103.
Ochi T Sakamoto M Minamida A Suzuki K Ueda T Une T Toda H Matsumoto K Terauchi Y 《Bioorganic & medicinal chemistry letters》2005,15(4):1055-1059
Two major metabolites in humans of blonanserin, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta-[b]pyridine (code name AD-5423), were synthesized. The first, 7-hydroxylated AD-5423, was synthesized through a four-step process starting from 4-fluorobenzoylacetonitrile (1), and the second, 8-hydroxylated AD-5423, a nine-step process also from 1. The optical resolution, structures, and receptor binding properties of the metabolites were documented. 相似文献
104.
Cell-to-cell movement of the CAPRICE protein in Arabidopsis root epidermal cell differentiation 总被引:5,自引:0,他引:5
Kurata T Ishida T Kawabata-Awai C Noguchi M Hattori S Sano R Nagasaka R Tominaga R Koshino-Kimura Y Kato T Sato S Tabata S Okada K Wada T 《Development (Cambridge, England)》2005,132(24):5387-5398
CAPRICE (CPC), a small, R3-type Myb-like protein, is a positive regulator of root hair development in Arabidopsis. Cell-to-cell movement of CPC is important for the differentiation of epidermal cells into trichoblasts (root hair cells). CPC is transported from atrichoblasts (hairless cells), where it is expressed, to trichoblasts, and generally accumulates in their nuclei. Using truncated versions of CPC fused to GFP, we identified a signal domain that is necessary and sufficient for CPC cell-to-cell movement. This domain includes the N-terminal region and a part of the Myb domain. Amino acid substitution experiments indicated that W76 and M78 in the Myb domain are critical for targeted transport, and that W76 is crucial for the nuclear accumulation of CPC:GFP. To evaluate the tissue-specificity of CPC movement, CPC:GFP was expressed in the stele using the SHR promoter and in trichoblasts using the EGL3 promoter. CPC:GFP was able to move from trichoblasts to atrichoblasts but could not exit from the stele, suggesting the involvement of tissue-specific regulatory factors in the intercellular movement of CPC. Analyses with a secretion inhibitor, Brefeldin A, and with an rhd3 mutant defective in the secretion process in root epidermis suggested that intercellular CPC movement is mediated through plasmodesmata. Furthermore, the fusion of CPC to tandem-GFPs defined the capability of CPC to increase the size exclusion limit of plasmodesmata. 相似文献
105.
Tanaka T Ebata T Tajima A Kinoshita K Okumura K Yagita H 《Biochemical and biophysical research communications》2005,332(1):311-317
Blastocyst MHC is a mouse MHC class Ib gene that is selectively expressed in blastocysts and placenta like human HLA-G, which protect fetal trophoblasts and some tumor cells from NK cell attack, and in TAP-dependent expression on the cell surface. We expressed blastocyst MHC cDNA in beta2-deficient EL-4 S3 or beta2m-transfected EL-4 S3 cells. In parental EL-4 S3 cells, only 47-kDa blastocyst MHC protein was expressed and retained in the cytoplasm. However, additional 51-kDa blastocyst MHC protein was expressed on the surface of beta2m-transfected EL-4 S3 cells. The 51-kDa protein was resistant to Endo-H, whereas the 47-kDa protein was sensitive for Endo-H. The results suggested that beta2m as well as TAP was necessary for the transportation of blastocyst MHC from endoplasmic reticulum to cell surfaces through the Golgi apparatus, similar to other MHC class I molecules. 相似文献
106.
Kido T Arata S Suzuki R Hosono T Nakanishi Y Miyazaki J Saito I Kuroki T Shioda S 《Development, growth & differentiation》2005,47(1):15-24
The quality control of sperm is critical for efficient reproduction. In germ cells, cell death involves different processes to those in somatic cells, and in many cases, the trigger to induce cell death in deficient germ cells is still unclear. It is known that the fatty acid composition of sperm is related to fertility. Composition of the fatty acid of germ cells changes dynamically during spermatogenesis, and fatty acid binding protein (FABP) may be involved in these changes. In this study, we developed transgenic mice with a testicular germ-cell-specific FABP (PERF15) transgene, whose expression was controlled by the Cre-LoxP site-specific recombination system. We also developed transgenic mice with the Cre gene under the control of the spermatocyte specific Pgk2 promoter. In double transgenic mice, following Cre-mediated recombination of the PERF15 containing transgene, PERF15 was strongly overexpressed. Its overexpression induced multinucleate symplasts to form, indicating programmed germ cell death occurred at the elongated spermatid stage. As a result, sperm harboring the transgene were significantly decreased, but the surviving sperm demonstrated higher fertility than natural sperm. Therefore, we conclude that PERF15 associate with the direction of germ cell fates and preserve the quality of sperm. 相似文献
107.
108.
109.
RB3 is a neuron-specific homologue of the SCG10/stathmin family proteins, possessing a unique N-terminal membrane-associated domain and the stathmin-like domain at the C terminus, which promotes microtubule (MT) catastrophe and/or tubulin sequestering. We examined herein the contribution of the N-terminal subdomain of RB3 to the regulation of MT dynamics. To begin with, we determined the effects of full-length (RB3-f) and short truncated (RB3-s) forms of RB3 on the polymerization of MT in vitro. RB3-s had a deletion of amino acids 1-75 from the N terminus, leaving the so-called stathmin-like domain, consisting of residues 76-217. Although both RB3-f and RB3-s exhibited MT-depolymerizing activity, RB3-f was less effective. The binding affinity for tubulin was also lower in RB3-f. Direct observation of the dynamics of individual MTs using dark field microscopy revealed that RB3-s slowed MT elongation velocity, increased catastrophes, and reduced rescues. This effect is almost identical to that by stathmin/oncoprotein 18. On the other hand, the MT elongation rate increased at lower concentrations of RB3-f. In addition, RB3-f, indicated higher rescue frequency than control as well as the catastrophe in a dose-dependent manner. The functionality of RB3-f indicated that full-length RB3 has not only stathmin-like MT destabilizing activity but also MT-associated protein-like MT stabilizing activity. Possibly, the balance of these activities is altered in a concentration-dependent manner in vitro. This interesting regulatory role of the unique N-terminal domain of RB3 in MT dynamics would contribute to the physiological regulation of neuronal morphogenesis. 相似文献
110.
Nishikawa H Ooka S Sato K Arima K Okamoto J Klevit RE Fukuda M Ohta T 《The Journal of biological chemistry》2004,279(6):3916-3924
The breast and ovarian cancer suppressor BRCA1 acquires significant ubiquitin ligase activity when bound to BARD1 as a RING heterodimer. Although the activity may well be important for the role of BRCA1 as a tumor suppressor, the biochemical consequence of the activity is not yet known. Here we report that BRCA1-BARD1 catalyzes Lys-6-linked polyubiquitin chain formation. K6R mutation of ubiquitin dramatically reduces the polyubiquitin products mediated by BRCA1-BARD1 in vitro. BRCA1-BARD1 preferentially utilizes ubiquitin with a single Lys residue at Lys-6 or Lys-29 to mediate autoubiquitination of BRCA1 in vivo. Furthermore, mass spectrometry analysis identified the Lys-6-linked branched ubiquitin fragment from the polyubiquitin chain produced by BRCA1-BARD1 using wild type ubiquitin. The BRCA1-BARD1-mediated Lys-6-linked polyubiquitin chains are deubiquitinated by 26 S proteasome in vitro, whereas autoubiquitinated CUL1 through Lys-48-linked polyubiquitin chains is degraded. Proteasome inhibitors do not alter the steady state level of the autoubiquitinated BRCA1 in vivo. Hence, the results indicate that BRCA1-BARD1 mediates novel polyubiquitin chains that may be distinctly edited by 26 S proteasome from conventional Lys-48-linked polyubiquitin chains. 相似文献