53 research outputs found

    The Canine Papillomavirus and Gamma HPV E7 Proteins Use an Alternative Domain to Bind and Destabilize the Retinoblastoma Protein

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    The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human cervical cells and the E7 protein can independently transform fibroblasts in vitro, primarily due to its ability to associate with and degrade the retinoblastoma tumor suppressor protein, pRb. The binding of E7 to pRb is mediated by a conserved Leu-X-Cys-X-Glu (LXCXE) motif in the conserved region 2 (CR2) of E7 and this domain is both necessary and sufficient for E7/pRb association. In the current study, we report that the E7 protein of the malignancy-associated canine papillomavirus type 2 encodes an E7 protein that has serine substituted for cysteine in the LXCXE motif. In HPV, this substitution in E7 abrogates pRb binding and degradation. However, despite variation at this critical site, the canine papillomavirus E7 protein still bound and degraded pRb. Even complete deletion of the LXSXE domain of canine E7 failed to interfere with binding to pRb in vitro and in vivo. Rather, the dominant binding site for pRb mapped to the C-terminal domain of canine E7. Finally, while the CR1 and CR2 domains of HPV E7 are sufficient for degradation of pRb, the C-terminal region of canine E7 was also required for pRb degradation. Screening of HPV genome sequences revealed that the LXSXE motif of the canine E7 protein was also present in the gamma HPVs and we demonstrate that the gamma HPV-4 E7 protein also binds pRb in a similar way. It appears, therefore, that the type 2 canine PV and gamma-type HPVs not only share similar properties with respect to tissue specificity and association with immunosuppression, but also the mechanism by which their E7 proteins interact with pRb

    Steroidal sapogenins from leaves of cordyline species

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    The steroidal sapogenins obtained by hydrolysis of the saponins found in the leaves of eight species of Cordyline have been studied. With the exception of C. terminalis var. petiolaris, the extracts of all species yielded 1,3-dihydroxy sapogenins, which were usually the predominant compounds. C. terminalis var. petiolaris differed from all the other species examined, not only because of its lack of dihydroxy sapogenins, but also because it yielded the 5β-spirostanes, sarsasapogenin and smilagenin. The extracts of all seven other species contained only 5α-sapogenins. Compounds detected were 3-epf-tigogenin, 3-epf-neotigogenin, tigogenin, neotigogenin, diosgenin, yamogenin, cannigenin, cordylagenin, brisbagenin, ruscogenin and 255-ruscogenin

    Crabbogenin, 1β-hydroxycrabbogenin, strictagenin and pompeygenin, four new steroidal sapogenins from cordyline stricta leaves

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    From the leaves of Cordyline stricia Endl. four new steroidal sapogenins crabbogenin {5α-spirost-25(27)-en-3α-ol}, 1β-hydroxycrabbogenin, strictagenin {(20S, 22S, 25S)-5α-furostan-22, 25-epoxy-1β, 3α, 26-triol} and pompeygenin {(25S)-5α-spirostane-1β, 3α-25-triol} have been isolated and their structures determined by chemical and spectroscopic methods

    Brisbagenin and brisbenone, two new spirostanes from Cordyline species

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    From the leaves of Cordyline cannifolia R.Br., a new steroidal sapogenin diol has been isolated, to which the trivial name brisbagenin has been given. Mass spectral, infra-red and nuclear magnetic resonance data of brisbagenin and its acetylated derivatives showed. the sapogenin to be 1β, 3β-dihydroxy-5α, 25α-spirostane. Jones oxidation of brisbagenin-1-acetate yielded 5α,25α-spirost-1-en-3-one. A compound, identical to this synthetic material was isolated from the leaves of an undescribed Cordyline species, but the product was considered to be an artefact produced during its isolation
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