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  • 1
    Online Resource
    Online Resource
    Activation of Peroxisome Proliferator-Activated Receptor γ Does Not Inhibit IL-6 or TNF-α Responses of Macrophages to Lipopolysaccharide In Vitro or In Vivo
    The American Association of Immunologists ; 2000
    In:  The Journal of Immunology Vol. 164, No. 2 ( 2000-01-15), p. 1046-1054
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 164, No. 2 ( 2000-01-15), p. 1046-1054
    Abstract: We have investigated the potential use of peroxisome proliferator-activated receptor γ (PPARγ) agonists as anti-inflammatory agents in cell-based assays and in a mouse model of endotoxemia. Human peripheral blood monocytes were treated with LPS or PMA and a variety of PPARγ agonists. Although 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) at micromolar concentrations significantly inhibited the production of TNF-α and IL-6, four other high affinity PPARγ ligands failed to affect cytokine production. Similar results were obtained when the monocytes were allowed to differentiate in culture into macrophages that expressed significantly higher levels of PPARγ or when the murine macrophage cell line RAW 264.7 was used. Furthermore, saturating concentrations of a potent PPARγ ligand not only failed to block cytokine production, but also were unable to block the inhibitory activity of 15d-PGJ2. Thus, activation of PPARγ does not appear to inhibit the production of cytokines by either monocytes or macrophages, and the inhibitory effect observed with 15d-PGJ2 is most likely mediated by a PPARγ-independent mechanism. To examine the anti-inflammatory activity of PPARγ agonists in vivo, db/db mice were treated with a potent thiazolidinedione that lowered their elevated blood glucose and triglyceride levels as expected. When thiazolidinedione-treated mice were challenged with LPS, they displayed no suppression of cytokine production. Rather, their blood levels of TNF-α and IL-6 were elevated beyond the levels observed in control db/db mice challenged with LPS. Comparable results were obtained with the corresponding lean mice. Our data suggest that compounds capable of activating PPARγ in leukocytes will not be useful for the treatment of acute inflammation.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.164.2.1046
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2000
    detail.hit.zdb_id: 1475085-5
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  • 2
    Online Resource
    Online Resource
    Protein interaction analysis of SCF ubiquitin E3 ligase subunits from Arabidopsis
    Wiley ; 2003
    In:  The Plant Journal Vol. 34, No. 6 ( 2003-06), p. 753-767
    Details
    In: The Plant Journal, Wiley, Vol. 34, No. 6 ( 2003-06), p. 753-767
    Abstract: Ubiquitin E3 ligases are a diverse family of protein complexes that mediate the ubiquitination and subsequent proteolytic turnover of proteins in a highly specific manner. Among the several classes of ubiquitin E3 ligases, the Skp1‐Cullin‐F‐box (SCF) class is generally comprised of three ‘core’ subunits: Skp1 and Cullin, plus at least one F‐box protein (FBP) subunit that imparts specificity for the ubiquitination of selected target proteins. Recent genetic and biochemical evidence in Arabidopsis thaliana suggests that post‐translational turnover of proteins mediated by SCF complexes is important for the regulation of diverse developmental and environmental response pathways. In this report, we extend upon a previous annotation of the Arabidopsis Skp1‐like (ASK) and FBP gene families to include the Cullin family of proteins. Analysis of the protein interaction profiles involving the products of all three gene families suggests a functional distinction between ASK proteins in that selected members of the protein family interact generally while others interact more specifically with members of the F‐box protein family. Analysis of the interaction of Cullins with FBPs indicates that CUL1 and CUL2, but not CUL3A, persist as components of selected SCF complexes, suggesting some degree of functional specialization for these proteins. Yeast two‐hybrid analyses also revealed binary protein interactions between selected members of the FBP family in Arabidopsis . These and related results are discussed in terms of their implications for subunit composition, stoichiometry and functional diversity of SCF complexes in Arabidopsis .
    Type of Medium: Online Resource
    ISSN: 0960-7412 , 1365-313X
    URL: Article
    DOI: 10.1046/j.1365-313X.2003.01768.x
    Language: English
    Publisher: Wiley
    Publication Date: 2003
    detail.hit.zdb_id: 2020961-7
    SSG: 12
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  • 3
    Online Resource
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    Targeted degradation of TOC1 by ZTL modulates circadian function in Arabidopsis thaliana
    Springer Science and Business Media LLC ; 2003
    In:  Nature Vol. 426, No. 6966 ( 2003-12), p. 567-570
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 426, No. 6966 ( 2003-12), p. 567-570
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/nature02163
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2003
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 4
    Online Resource
    Online Resource
    ZEITLUPE Encodes a Novel Clock-Associated PAS Protein from Arabidopsis
    Elsevier BV ; 2000
    In:  Cell Vol. 101, No. 3 ( 2000-04), p. 319-329
    Details
    In: Cell, Elsevier BV, Vol. 101, No. 3 ( 2000-04), p. 319-329
    Type of Medium: Online Resource
    ISSN: 0092-8674
    URL: Article
    DOI: 10.1016/S0092-8674(00)80841-7
    RVK:
    XA 36269
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2000
    detail.hit.zdb_id: 187009-9
    detail.hit.zdb_id: 2001951-8
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Cloning of the Arabidopsis Clock Gene TOC1 , an Autoregulatory Response Regulator Homolog
    American Association for the Advancement of Science (AAAS) ; 2000
    In:  Science Vol. 289, No. 5480 ( 2000-08-04), p. 768-771
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 289, No. 5480 ( 2000-08-04), p. 768-771
    Abstract: The toc1 mutation causes shortened circadian rhythms in light-grown Arabidopsis plants. Here, we report the same toc1 effect in the absence of light input to the clock. We also show that TOC1 controls photoperiodic flowering response through clock function. The TOC1 gene was isolated and found to encode a nuclear protein containing an atypical response regulator receiver domain and two motifs that suggest a role in transcriptional regulation: a basic motif conserved within the CONSTANS family of transcription factors and an acidic domain. TOC1 is itself circadianly regulated and participates in a feedback loop to control its own expression.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.289.5480.768
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2000
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 6
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    Online Resource
    Clock-associated genes in Arabidopsis : a family affair
    The Royal Society ; 2001
    In:  Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences Vol. 356, No. 1415 ( 2001-11-29), p. 1745-1753
    Details
    In: Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, The Royal Society, Vol. 356, No. 1415 ( 2001-11-29), p. 1745-1753
    Abstract: The identification of components of the plant circadian clock has been advanced recently with the success of two forward genetics approaches. The ZEITLUPE and TOC1 loci were cloned and each was found to be part of two separate, larger gene families with intriguing domain structures. The ZTL family of proteins contains a subclass of the PAS domain coupled to an F box and kelch motifs, suggesting that they play a role in a novel light–regulated ubiquitination mechanism. TOC1 shares similarity to the receiver domain of the well–known two–component phosphorelay signalling systems, combined with a strong similarity to a region of the CONSTANS transcription factor, which is involved in controlling flowering time. When added to the repertoire of previously identified clock–associated genes, it is clear that both similarities and differences with other circadian systems will emerge in the coming years.
    Type of Medium: Online Resource
    ISSN: 0962-8436 , 1471-2970
    URL: Article
    DOI: 10.1098/rstb.2001.0965
    RVK:
    WA 15000
    Language: English
    Publisher: The Royal Society
    Publication Date: 2001
    detail.hit.zdb_id: 1462620-2
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Formation of an SCF ZTL complex is required for proper regulation of circadian timing
    Wiley ; 2004
    In:  The Plant Journal Vol. 40, No. 2 ( 2004-10), p. 291-301
    Details
    In: The Plant Journal, Wiley, Vol. 40, No. 2 ( 2004-10), p. 291-301
    Abstract: The circadian timing system involves an autoregulatory transcription/translation feedback loop that incorporates a diverse array of factors to maintain a 24‐h periodicity. In Arabidopsis a novel F‐box protein, ZEITLUPE (ZTL), plays an important role in the control of the free‐running period of the circadian clock. As a class, F‐box proteins are well‐established components of the Skp/Cullin/F‐box (SCF) class of E3 ubiquitin ligases that link the target substrates to the core ubiquitinating activity of the ligase complex via direct association with the Skp protein. Here we identify and characterize the SCF ZTL complex in detail. Yeast two‐hybrid tests demonstrate the sufficiency and necessity of the F‐box domain for Arabidopsis Skp‐like protein (ASK) interactions and the dispensability of the unique N‐terminal LOV domain in this association. Co‐immunoprecipitation of full‐length (FL) ZTL with the three known core components of SCF complexes (ASK1, AtCUL1 and AtRBX1) demonstrates that ZTL can assemble into an SCF complex in vivo . F‐box‐containing truncated versions of ZTL (LOV‐F and F‐kelch) can complex with SCF components in vivo , whereas stably expressed LOV or kelch domains alone cannot. Stable expression of F‐box‐mutated FL ZTL eliminates the shortened period caused by mild ZTL overexpression and also abolishes ASK1 interaction in vivo . Reduced levels of the core SCF component AtRBX1 phenocopy the long period phenotype of ztl loss‐of‐function mutations, demonstrating the functional significance of the SCF ZTL complex. Taken together, our data establish SCF ZTL as an essential SCF class E3 ligase controlling circadian period in plants.
    Type of Medium: Online Resource
    ISSN: 0960-7412 , 1365-313X
    URL: Issue
    URL: Article
    DOI: 10.1111/tpj.2004.40.issue-2
    DOI: 10.1111/j.1365-313X.2004.02207.x
    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 2020961-7
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  • 8
    Online Resource
    Online Resource
    The F-Box Protein ZEITLUPE Confers Dosage-Dependent Control on the Circadian Clock, Photomorphogenesis, and Flowering Time[W]
    Oxford University Press (OUP) ; 2004
    In:  The Plant Cell Vol. 16, No. 3 ( 2004-03-04), p. 769-782
    Details
    In: The Plant Cell, Oxford University Press (OUP), Vol. 16, No. 3 ( 2004-03-04), p. 769-782
    Abstract: As an F-box protein, ZEITLUPE (ZTL) is involved in targeting one or more substrates for ubiquitination and degradation via the proteasome. The initial characterization of ZTL suggested a function limited largely to the regulation of the circadian clock. Here, we show a considerably broader role for ZTL in the control of circadian period and photomorphogenesis. Using a ZTL-specific antibody, we quantitated and characterized a ZTL dosage series that ranges from a null mutation to a strong ZTL overexpressor. In the dark,ztl null mutations lengthen circadian period, and overexpression causes arrhythmicity, suggesting a more comprehensive role for this protein in the clock than previously suspected. In the light, circadian period becomes increasingly shorter at higher levels of ZTL, to the point of arrhythmicity. By contrast, hypocotyl length increases and flowering time is delayed in direct proportion to the level of ZTL. We propose a novel testable mechanism by which circadian period and amplitude may act together to gate phytochrome B–mediated suppression of hypocotyl. We also demonstrate that ZTL-dependent delay of flowering is mediated through decreases in CONSTANS and FLOWERING LOCUS T message levels, thus directly linking proteasome-dependent proteolysis to flowering.
    Type of Medium: Online Resource
    ISSN: 1532-298X
    URL: Article
    DOI: 10.1105/tpc.016808
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2004
    detail.hit.zdb_id: 623171-8
    detail.hit.zdb_id: 2004373-9
    SSG: 12
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  • 9
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    Online Resource
    Circadian phase-specific degradation of the F-box protein ZTL is mediated by the proteasome
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 8 ( 2003-04-15), p. 4933-4938
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 8 ( 2003-04-15), p. 4933-4938
    Abstract: Critical to the maintenance of circadian rhythmicity is the cyclic expression of at least some components of the central oscillator. High-amplitude cycling of mRNA and protein abundance, protein phosphorylation and nuclear/cytoplasmic shuttling have all been implicated in the maintenance of circadian period. Here we use a newly characterized Arabidopsis suspension cell culture to establish that the rhythmic changes in the levels of the clock-associated F-box protein, ZTL, are posttranscriptionally controlled through different circadian phase-specific degradation rates. This proteolysis is proteasome dependent, implicating ZTL itself as substrate for ubiquitination. This demonstration of circadian phase-regulated degradation of an F-box protein, which itself controls circadian period, suggests a novel regulatory feedback mechanism among known circadian systems.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0736949100
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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  • 10
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    Pivotal Research in Cardiovascular Syndromes in the Elderly
    Wiley ; 2000
    In:  The American Journal of Geriatric Cardiology Vol. 9, No. 5 ( 2000-09), p. 243-251
    Details
    In: The American Journal of Geriatric Cardiology, Wiley, Vol. 9, No. 5 ( 2000-09), p. 243-251
    Abstract: The PRICE‐1 conference was designed to identify near term priorities for funding cardiovascular research in the elderly. Twenty topics were identified with either break throughs in fundamental mechanisms of aging with cardiovascular systems or with critical importaance to cardiovascular carve of the elderly.
    Type of Medium: Online Resource
    ISSN: 1076-7460 , 1751-715X
    URL: Issue
    URL: Article
    DOI: 10.1111/agc.2000.9.issue-5
    DOI: 10.1111/j.1076-7460.2000.89991.x
    Language: English
    Publisher: Wiley
    Publication Date: 2000
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