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21.
22.
Recent results from several laboratories suggest that the interaction of E2 ubiquitin-conjugating enzymes with the RING finger domain has a central role in mediating the transfer of ubiquitin to proteins. Here we present a mutational analysis of the interaction between the E2 enzyme UbcM4/UbcH7 and three different RING finger proteins, termed UIPs, which, like Parkin, contain a RING1-IBR-RING2 motif. The results show that the E2 enzyme binds to the RING1 domain but not to the other cysteine/histidine-rich domains of the RING1-IBR-RING2 motif. Three regions within the UbcM4 molecule are involved in this interaction: the H1 alpha helix, loop L1, connecting the third and fourth strand of the beta sheet, and loop L2, located between the fourth beta strand and the second alpha helix. Loop L2 plays an important role in determining the specificity of interaction. The effects of L2 mutations on UbcM4/UIP interaction are different for each UIP, indicating that RING finger domains can vary considerably in their structural requirements for binding to E2 enzymes. The result that single amino-acid changes can regulate binding of E2 enzymes to different RING finger proteins suggests a novel approach to experimentally manipulate proteolytic pathways mediated by RING finger proteins. 相似文献
23.
Differentiation-associated modulation of heparan sulfate structure and function in CaCo-2 colon carcinoma cells 总被引:3,自引:2,他引:1
Salmivirta M; Safaiyan F; Prydz K; Andresen MS; Aryan M; Kolset SO 《Glycobiology》1998,8(10):1029-1036
Heparan sulfate species expressed by different cell and tissue types differ
in their structural and functional properties. Limited information is
available on differences in regulation of heparan sulfate biosynthesis
within a single tissue or cell population under different conditions. We
have approached this question by studying the effect of cell
differentiation on the biosynthesis and function of heparan sulfate in
human colon carcinoma cells (CaCo-2). These cells undergo spontaneous
differentiation in culture when grown on semipermeable supports; the
differentiated cells show phenotypic similarity to small intestine
enterocytes. Metabolically labeled heparan sulfate was isolated from the
apical and basolateral media from cultures of differentiated and
undifferentiated cells. Compositional analysis of disaccharides, derived
from the contiguous N-sulfated regions of heparan sulfate, indicated a
greater proportion of 2-O- sulfated iduronic acid units and a smaller
amount of 6-O-sulfated glucosamine units in differentiated than in
undifferentiated cells. By contrast, the overall degree of sulfation, the
chain length and the size distribution of the N-acetylated regions were
similar regardless the differentiation status of the cells. The structural
changes were found to affect the binding of heparan sulfate to the long
isoform of platelet-derived growth factor A chain but not to fibroblast
growth factor 2. These findings show that heparan sulfate structures change
during cell differentiation and that heparan sulfate-growth factor
interactions may be affected by such changes.
相似文献
24.
Serglycin is the major proteoglycan in most hematopoietic cells, including
monocytes and macrophages. The monoblastic cell line U937-1 was used to
study the expression of serglycin during proliferation and differentiation.
In unstimulated proliferating U937-1 cells serglycin mRNA is
nonconstitutively expressed. The level of serglycin mRNA was found to
correlate with the synthesis of chondroitin sulfate proteoglycan (CSPG).
The U937-1 cells were induced to differentiate into different types of
macrophage-like cells by exposing the cells to PMA, RA, or VitD3. These
inducers of differentiation affected the expression of serglycin mRNA in
three different ways. The initial upregulation seen in the normally
proliferating cells was not observed in PMA treated cells. In contrast, RA
increased the initial upregulation, giving a reproducible six times
increase in serglycin mRNA level from 4 to 24 h of incubation, compared to
a four times increase in the control cells. VitD3 had no effect on the
expression of serglycin mRNA. The incorporation of (35S)sulfate into CSPG
decreased approximately 50% in all three differentiated cell types.
Further, the (35S)CSPGs expressed were of larger size in PMA treated cells
than controls, but smaller after RA treatment. This was due to the
expression of CSPGs, with CS-chains of 25 and 5 kDa in PMA and RA treated
cells, respectively, compared to 11 kDa in the controls. VitD3 had no
significant effect on the size of CSPG produced. PMA treated cells secreted
75% of the (35S)PGs expressed, but the major portion was retained in cells
treated with VitD3 or RA. The differences seen in serglycin mRNA levels,
the macromolecular properties of serglycin and in the PG secretion
patterns, suggest that serglycin may have different functions in different
types of macrophages.
相似文献
25.
Infectivity and structure of molecular clones obtained from two genetically transmitted Moloney leukemia proviral genomes. 总被引:10,自引:1,他引:9
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The Mov-2 and Mov-10 substrains of mice, each carrying Moloney leukemia virus (= M-MuLV) in their germ line at the Mov-2 and Mov-10 locus, respectively, do occasionally at a later age (Mov-2) or not at all (Mov-10) activate infectious virus. The M-MuLV proviruses with flanking mouse sequences corresponding to the Mov-2 and Mov-10 locus, respectively, were molecularly cloned. Restriction enzyme analysis revealed no major deletions or insertions in the proviral genomes of the Mov-2 and Mov-10 locus. Both cloned DNAs induced XC plaques in a transfection assay. The specific infectivity, however, was very low and 3T3 cells transfected with the Mov-2 or Mov-10 clone did not produce infectious virus. Removing part of the 5' cellular sequences from the Mov-10 clone did not increase the infectivity. The results suggest that the M-MuLV integrated at the Mov-2 and Mov-10 locus carry a mutation which prevents synthesis of infectious virus but permits XC plaque induction by partial genome expression or synthesis of non-infectious particles. 相似文献
26.
27.
Libraries enriched for alternatively spliced exons reveal splicing patterns in melanocytes and melanomas 总被引:2,自引:0,他引:2
Watahiki A Waki K Hayatsu N Shiraki T Kondo S Nakamura M Sasaki D Arakawa T Kawai J Harbers M Hayashizaki Y Carninci P 《Nature methods》2004,1(3):233-239
It is becoming increasingly clear that alternative splicing enables the complex development and homeostasis of higher organisms. To gain a better understanding of how splicing contributes to regulatory pathways, we have developed an alternative splicing library approach for the identification of alternatively spliced exons and their flanking regions by alternative splicing sequence enriched tags sequencing. Here, we have applied our approach to mouse melan-c melanocyte and B16-F10Y melanoma cell lines, in which 5,401 genes were found to be alternatively spliced. These genes include those encoding important regulatory factors such as cyclin D2, Ilk, MAPK12, MAPK14, RAB4, melastatin 1 and previously unidentified splicing events for 436 genes. Real-time PCR further identified cell line-specific exons for Tmc6, Abi1, Sorbs1, Ndel1 and Snx16. Thus, the ASL approach proved effective in identifying splicing events, which suggest that alternative splicing is important in melanoma development. 相似文献
28.
Residuals for multinomial models 总被引:1,自引:0,他引:1
29.
SO Akarca-Dizakar H Aktuğ F Oltulu G Öktem A Yavaşoğlu E Açikgöz 《Biotechnic & histochemistry》2013,88(5):328-335
Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We investigated the possible effects of sunitinib on the kidney of streptozotocin (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1 was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment. Kidneys were removed after 8 weeks. The immunoreactivities of vimentin, E-cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100 was located in both the glomeruli and tubules of the kidney. We found that the number of vimentin and E-cadherin positive glomeruli and tubules were increased after sunitinib treatment compared to saline treated diabetic mice. The number of vimentin labeled tubules was decreased in the sunitinib treated group compared to diabetic + saline groups. Differences in the number of S100 positive tubules and glomeruli between groups 3 and 4 were not statistically significant. The effect of sunitinib on experimental diabetic mice appears to be related to levels of vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and sunitinib may protect against renal damage from DM. 相似文献
30.
KH Konopka M Harbers A Houghton R Kortekaas A van Vliet W Timmerman JA den Boer MM Struys M van Wijhe 《PloS one》2012,7(8):e43526
Due to the lack of a specific diagnostic tool for neuropathic pain, a grading system to categorize pain as 'definite', 'probable', 'possible' and 'unlikely' neuropathic was proposed. Somatosensory abnormalities are common in neuropathic pain and it has been suggested that a greater number of abnormalities would be present in patients with 'probable' and 'definite' grades. To test this hypothesis, we investigated the presence of somatosensory abnormalities by means of Quantitative Sensory Testing (QST) in patients with a clinical diagnosis of neuropathic pain and correlated the number of sensory abnormalities and sensory profiles to the different grades. Of patients who were clinically diagnosed with neuropathic pain, only 60% were graded as 'definite' or 'probable', while 40% were graded as 'possible' or 'unlikely' neuropathic pain. Apparently, there is a mismatch between a clinical neuropathic pain diagnosis and neuropathic pain grading. Contrary to the expectation, patients with 'probable' and 'definite' grades did not have a greater number of abnormalities. Instead, similar numbers of somatosensory abnormalities were identified for each grade. The profiles of sensory signs in 'definite' and 'probable' neuropathic pain were not significantly different, but different from the 'unlikely' grade. This latter difference could be attributed to differences in the prevalence of patients with a mixture of sensory gain and loss and with sensory loss only. The grading system allows a separation of neuropathic and non-neuropathic pain based on profiles but not on the total number of sensory abnormalities. Our findings indicate that patient selection based on grading of neuropathic pain may provide advantages in selecting homogenous groups for clinical research. 相似文献