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351.
Seiichi Sato Yingshe Zhao Misa Imai Philip C. Simister Stephan M. Feller Philip C. Trackman Kathrin H. Kirsch Gail E. Sonenshein 《PloS one》2013,8(10)
The lysyl oxidase gene inhibits Ras signaling in transformed fibroblasts and breast cancer cells. Its activity was mapped to the 162 amino acid propeptide domain (LOX-PP) of the lysyl oxidase precursor protein. LOX-PP inhibited the Her-2/Ras signaling axis in breast cancer cells, and reduced the Her-2-driven breast tumor burden in a xenograft model. Since its mechanism of action is largely unknown, co-affinity-purification/mass spectrometry was performed and the “Cbl-interacting protein of 85-kDa” (CIN85) identified as an associating protein. CIN85 is an SH3-containing adapter protein that is overexpressed in invasive breast cancers. The CIN85 SH3 domains interact with c-Cbl, an E3 ubiquitin ligase, via an unconventional PxxxPR ligand sequence, with the highest affinity displayed by the SH3-B domain. Interaction with CIN85 recruits c-Cbl to the AMAP1 complex where its ubiquitination activity is necessary for cancer cells to develop an invasive phenotype and to degrade the matrix. Direct interaction of LOX-PP with CIN85 was confirmed using co-immunoprecipitation analysis of lysates from breast cancer cells and of purified expressed proteins. CIN85 interaction with c-Cbl was reduced by LOX-PP. Domain specific CIN85 regions and deletion mutants of LOX-PP were prepared and used to map the sites of interaction to the SH3-B domain of CIN85 and to an epitope encompassing amino acids 111 to 116 of LOX-PP. Specific LOX-PP point mutant proteins P111A and R116A failed to interact with CIN85 or to compete for CIN85 binding with c-Cbl. Structural modeling identified a new atypical PxpxxRh SH3-binding motif in this region of LOX-PP. The LOX-PP interaction with CIN85 was shown to reduce the invasive phenotype of breast cancer cells, including their ability to degrade the surrounding extracellular matrix and for Matrigel outgrowth. Thus, LOX-PP interacts with CIN85 via a novel SH3-binding motif and this association reduces CIN85-promoted invasion by breast cancer cells. 相似文献
352.
K. Suzuki Jürgen Henke Misa Iwata Lotte Henke Hiroko Tsuji Tatsushige Fukunaga Goichi Ishimoto Maria Szekelyi Shigenori Ito 《Human genetics》1996,98(4):393-395
Novel polymorphic sites within the coding region of the human coagulation factor XIII A-subunit (F13A) gene and their haplotypic
combinations with the other polymorphic sites thus far reported are presented. Polymorphic bands were detected in exons 2,
5, 8, 12 and 14 by using single strand conformational polymorphism analysis and antithetic forms of the polymorphic exons
were linked with each other, cosegregating as distinct sequence haplotypes. In Finnish, German, and Russian populations a
total of 18 haplotypes were observed of possible 72 haplotypic combinations of the 5 exons. Ten of the haplotypes detected
were found to have no novel mutations but to be only combinations of preexisting mutations. No tightly associated combinations
in pairwise comparisons between antithetic forms of the polymorphic exons were observed, indicating that there may be recombinational
hotspots within the F13A gene region.
Received: 10 November 1995 / Revised: 2 May 1996 相似文献
353.
Koichi Ushizawa Toru Takahashi Misa Hosoe Keiichiro Kizaki Yasuyuki Abe Hiroshi Sasada Eimei Sato Kazuyoshi Hashizume 《BMC developmental biology》2007,7(1):16
Background
This study reports the identification of a full-length cDNA sequence for two novel caprine prolactin-related proteins (cPRP1 and cPRP6), and their localization and quantitative expression in the placenta. Caprine PRPs are compared with known bovine PRPs. We examined their evolution and role in the ruminant placenta. 相似文献354.
355.
H. Lee K. Takahashi Y. Kodera K. Ohwada T. Tsuzuki A. Matsushima Y. Inada 《Biotechnology letters》1988,10(6):403-407
Summary Papain modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2) was soluble in benzene and retained the enzymic activity. Acid-amide bond formation by the modified enzyme proceeded efficiently in benzene; N-benzoyl-L-alanine alkylamides were synthesized from N-benzoyl-L-alanine methyl ester and various alkylamines, and N-benzoyl-L-alaninyl(oligo)leucine ethyl ester was formed from N-benzoyl-L-alanine methyl ester and L-leucine ethyl ester. 相似文献
356.
357.
Reduction of immunoreactivity of bovine serum albumin conjugated with polyethylene glycol(PEG) in relation to its esterase activity. 总被引:1,自引:0,他引:1
Bovine serum albumin was modified with activated PEG2, 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine. The PEG-modified albumin, in which 15 out of the total 60 amino groups in the albumin molecule were coupled with activated PEG2, lost immunoreactivity towards anti-albumin serum and retained 63% of the esterase activity of native albumin. 相似文献
358.
Chemical modification of L-asparaginase with a comb-shaped copolymer of polyethylene glycol derivative and maleic anhydride. 总被引:1,自引:0,他引:1
Y Kodera H Tanaka A Matsushima Y Inada 《Biochemical and biophysical research communications》1992,184(1):144-148
L-Asparaginase from Escherichia coli, an anti-tumor enzyme, was chemically modified with two types of maleic anhydride copolymers with a comb-shaped form, the one composed of polyoxyethylene allyl methyl diether with the molecular weight of 13,000 (activated PM13) and the other of polyoxyethylene 2-methyl-2-propenyl methyl diether with 100,000 (activated PM100). The modified asparaginases (PM13- and PM100-asparaginases) exhibited the complete loss of immunoreactivity towards anti-asparaginase serum. The enzymic activity of PM100-asparaginase without immunoreactivity was well retained by 85% of non-modified one, while that of PM13-asparaginase was retained 46%. These results were discussed in relation to the chemical structure of modifying reagents including chain shaped-polyethylene glycol derivatives. 相似文献
359.
Root explants ofArabidopsis thaliana ecotype C24 were bombarded with the plasmid pCH harboring the hygromycin phosphotransferase gene (hpt). A selection condition with post-bombardment culture of 3 days followed by culture with 20 mgl−1 hygromycin gave the highest yield of transformants. More than 44% of explant clumps formed transformant shoots. 相似文献
360.
Conformational analyses on four cyclic model peptides of the beta-bend, cyclo(L- or D-Phe-L-Pro-epsilon-aminocaproyl(Aca] and cyclo(L-Pro-L- or D-Phe-Aca), were carried out both experimentally and theoretically. Cyclo(D-Phe-L-Pro-Aca) was shown to exist as a single conformer taking the type II' beta-bend. The comparison of its CD spectra with those of cyclo(L-Ala-L-Ala-Aca) revealed that type I and II' beta-bends, both with alpha-helix-like CD spectra, can be distinguished. Cyclo(L-Phe-L-Pro-Aca) was shown to exist as a single conformer with a cis L-Phe-L-Pro peptide bond, taking the type VI beta-bend. Its CD spectrum has thus been observed for the first time for the bend containing a cis peptide bond. Cyclo(L-Pro-L-Phe-Aca) was shown to exist as a mixture of two conformers, the major one taking the type I beta-bend with a trans Aca-L-Pro peptide bond and the minor one with a cis Aca-L-Pro peptide bond. Cyclo(L-Pro-D-Phe-Aca) was suggested to exist as a mixture of two conformers, the major one taking the type II beta-bend with a trans Aca-L-Pro peptide bond and the minor one with a cis Aca-L-Pro peptide bond. 相似文献