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| 2. |
- Lerner, M, et al.
(författare)
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The RBCC gene RFP2 (Leu5) encodes a novel transmembrane E3 ubiquitin ligase involved in ERAD
- 2007
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Ingår i: Molecular biology of the cell. - : American Society for Cell Biology (ASCB). - 1059-1524 .- 1939-4586. ; 18:5, s. 1670-1682
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Tidskriftsartikel (refereegranskat)abstract
- RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins. Here we demonstrate that Rfp2 is an unstable protein with auto-polyubiquitination activity in vivo and in vitro, implying that Rfp2 acts as a RING E3 ubiquitin ligase. Consequently, Rfp2 ubiquitin ligase activity is dependent on an intact RING domain, as RING deficient mutants fail to drive polyubiquitination in vitro and are stabilized in vivo. Immunopurification and tandem mass spectrometry enabled the identification of several putative Rfp2 interacting proteins localized to the endoplasmic reticulum (ER), including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). Importantly, we also show that Rfp2 regulates the degradation of the known ER proteolytic substrate CD3-δ, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein), establishing Rfp2 as a novel E3 ligase involved in ERAD. Finally, we show that Rfp2 contains a C-terminal transmembrane domain indispensable for its localization to the ER and that Rfp2 colocalizes with several ER-resident proteins as analyzed by high-resolution immunostaining. In summary, these data are all consistent with a function for Rfp2 as an ERAD E3 ubiquitin ligase.
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| 7. |
- McCormick, S. D., et al.
(författare)
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Endocrine disruption of parr-smolt transformation and seawater tolerance of Atlantic salmon by 4-nonylphenol and 17 beta-estradiol
- 2005
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Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480. ; 142:3, s. 280-288
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Tidskriftsartikel (refereegranskat)abstract
- Sex steroids are known to interfere with the parr-smolt transformation of anadromous salmonids, and environmental estrogens such as nonylphenol have recently been implicated in reduced returns of Atlantic salmon in the wild. To determine the endocrine pathways by which estrogenic compounds affect smolt development and seawater tolerance, groups of juvenile Atlantic salmon were injected with one of five doses (0.5, 2, 10, 40 or 150 mu g g(-1)) of branched 4-nonylphenol (NP), 2 mu g g(-1) of 17 beta-estradiol (E-2), or vehicle, during the parr-smolt transformation in April, and the treatment was repeated 4, 8, and 11 days after the first injection. Plasma was obtained for biochemical analysis 7 and 14 days after initiation of treatment. After 14 days of treatment, additional fish from each treatment group were exposed to seawater for 24 h to assess salinity tolerance. The E, treatment and the highest NP dose resulted in lower salinity tolerance and decreased plasma insulin-like growth factor I (IGF-I) levels, along with elevated levels of plasma vitellogenin and total calcium. Plasma growth hormone levels were elevated at intermediate NP doses only, and not affected by E-2. After 7 days, plasma thyroxine (T-4) levels decreased in a strong, dose-dependent manner in response to nonylphenol, but after 14 days, this suppressive effect of T-4 occurred at the highest NP dose only. Similarly, E-2 decreased plasma T-4 levels at 7, but not 14 days. Plasma 3,3',5-triodo-L-thyronine was reduced by E-2 and the highest NP dose after 7 and 14 days of treatment. Plasma cortisol levels were not affected by any of the treatments. The results indicate that the parr-smolt transformation and salinity tolerance can be compromised by exposure to estrogenic compounds. Suppression of plasma IGF-I levels is a likely endocrine pathway for the effects of estrogenic compounds on hypo-osmoregulatory capacity, and the detrimental effects of E2 and NP on thyroid hormone levels are also likely to compromise the normal parr-smolt transformation of Atlantic salmon. Published by Elsevier Inc.
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| 8. |
- Månsson, Wiking, et al.
(författare)
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Noncontinent urinary diversion
- 2006
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Ingår i: Textbook of Bladder Cancer. - 9781841843827 - 1841843822 ; , s. 607-607
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Brage, M, et al.
(författare)
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Different cysteine proteinases involved in bone resorption and osteoclast formation.
- 2005
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 76:6, s. 439-47
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Tidskriftsartikel (refereegranskat)abstract
- Cysteine proteinases, especially cathepsin K, play an important role in osteoclastic degradation of bone matrix proteins and the process can, consequently, be significantly inhibited by cysteine proteinase inhibitors. We have recently reported that cystatin C and other cysteine proteinase inhibitors also reduce osteoclast formation. However, it is not known which cysteine proteinase(s) are involved in osteoclast differentiation. In the present study, we compared the relative potencies of cystatins C and D as inhibitors of bone resorption in cultured mouse calvariae, osteoclastogenesis in mouse bone marrow cultures, and cathepsin K activity. Inhibition of cathepsin K activity was assessed by determining equilibrium constants for inhibitor complexes in fluorogenic substrate assays. The data demonstrate that whereas human cystatins C and D are equipotent as inhibitors of bone resorption, cystatin D is 10-fold less potent as an inhibitor of osteoclastogenesis and 200-fold less potent as an inhibitor of cathepsin K activity. A recombinant human cystatin C variant with Gly substitutions for residues Arg8, Leu9, Val10, and Trp106 did not inhibit bone resorption, had 1,000-fold decreased inhibitory effect on cathepsin K activity compared to wildtype cystatin C, but was equipotent with wildtype cystatin C as an inhibitor of osteoclastogenesis. It is concluded that (i) different cysteine proteinases are likely to be involved in bone resorption and osteoclast formation, (ii) cathepsin K may not be an exclusive target enzyme in any of the two systems, and (iii) the enzyme(s) involved in osteoclastogenesis might not be a typical papain-like cysteine proteinase.
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| 10. |
- Honig, Benson, et al.
(författare)
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Social capital and the linkages of high-tech companies to the military defense system : Is there a signaling mechanism?
- 2006
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Ingår i: Small Business Economics. - : Springer. - 0921-898X .- 1573-0913. ; 27:4-5, s. 419-437
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates linkages of new Israeli high-tech companies to the military and defense system. We examine the impact of social capital, signaling, and learning spillovers on resource acquisition in terms of investments and the financial performance of companies with and without linkages. Social capital, signaling, and learning spillovers are examined as they impact individual and organizational resource acquisition and performance of 200 new Israeli high-tech companies. The study contributes to the existing literature of entrepreneurship by suggesting the relevance of knowledge spillovers, signaling theory and social capital to the context of the interface between defense and civilian spheres.
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