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PMC:3148254 / 22085-27684 JSONTXT 18 Projects

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Id Subject Object Predicate Lexical cue
T149 0-10 Sentence denotes Discussion
T9192 11-121 Sentence denotes Our results indicate that the protein HOIP is critical for CD40-induced signals that regulate B cell function.
T150 11-121 Sentence denotes Our results indicate that the protein HOIP is critical for CD40-induced signals that regulate B cell function.
T9193 122-400 Sentence denotes Our data show that HOIP-dependent cellular responses include CD40-mediated upregulation of CD80 expression and synthesis of germline RNA transcripts from the immunoglobulin heavy chain locus, two events that are important for T-cell-dependent antibody-mediated immune responses.
T151 122-400 Sentence denotes Our data show that HOIP-dependent cellular responses include CD40-mediated upregulation of CD80 expression and synthesis of germline RNA transcripts from the immunoglobulin heavy chain locus, two events that are important for T-cell-dependent antibody-mediated immune responses.
T9194 401-598 Sentence denotes At the molecular level, our data indicate that HOIP functions downstream of TRAF2 in the CD40 signaling pathway and that HOIP has a key role in promoting the recruitment of the IKK complex to CD40.
T152 401-598 Sentence denotes At the molecular level, our data indicate that HOIP functions downstream of TRAF2 in the CD40 signaling pathway and that HOIP has a key role in promoting the recruitment of the IKK complex to CD40.
T9195 599-691 Sentence denotes Consistent with this, CD40-induced activation of NF-κB is dependent on the presence of HOIP.
T153 599-691 Sentence denotes Consistent with this, CD40-induced activation of NF-κB is dependent on the presence of HOIP.
T9196 692-794 Sentence denotes In addition, our data show that HOIP facilitates the activation of JNK in response to CD40 engagement.
T154 692-794 Sentence denotes In addition, our data show that HOIP facilitates the activation of JNK in response to CD40 engagement.
T9197 795-912 Sentence denotes Together, our findings provide support for the conclusion that HOIP is a key component of the CD40 signaling pathway.
T155 795-912 Sentence denotes Together, our findings provide support for the conclusion that HOIP is a key component of the CD40 signaling pathway.
T9198 913-1089 Sentence denotes Given the importance of CD40 signaling in both cellular and humoral immune responses, our results indicate that HOIP has a critical role in the regulation of the immune system.
T156 913-1089 Sentence denotes Given the importance of CD40 signaling in both cellular and humoral immune responses, our results indicate that HOIP has a critical role in the regulation of the immune system.
T9199 1090-1163 Sentence denotes The functional properties of HOIP have only been partially characterized.
T157 1090-1163 Sentence denotes The functional properties of HOIP have only been partially characterized.
T9200 1164-1337 Sentence denotes Initial studies showed that HOIP and the related protein HOIL-1 are components of a large (∼600 kDa) protein complex capable of synthesizing linear polyubiquitin chains [5].
T158 1164-1337 Sentence denotes Initial studies showed that HOIP and the related protein HOIL-1 are components of a large (∼600 kDa) protein complex capable of synthesizing linear polyubiquitin chains [5].
T9201 1338-1484 Sentence denotes Subsequent studies showed that a HOIP-containing complex can interact with IKKγ and facilitate activation of NF-κB via the canonical pathway [16].
T159 1338-1484 Sentence denotes Subsequent studies showed that a HOIP-containing complex can interact with IKKγ and facilitate activation of NF-κB via the canonical pathway [16].
T9202 1485-1626 Sentence denotes These data, considered together with ours, suggest that a HOIP-containing complex mediates recruitment of IKKγ to the CD40 signaling complex.
T160 1485-1626 Sentence denotes These data, considered together with ours, suggest that a HOIP-containing complex mediates recruitment of IKKγ to the CD40 signaling complex.
T9203 1627-1750 Sentence denotes In addition, CD40-associated HOIP could play a role in activating IKKγ after its recruitment to the signaling complex [16].
T161 1627-1750 Sentence denotes In addition, CD40-associated HOIP could play a role in activating IKKγ after its recruitment to the signaling complex [16].
T9204 1751-2040 Sentence denotes The higher molecular weight forms of IKKγ we observed in CD40 immunoprecipitates would be consistent with the presence of post-transcriptional modifications including phosphorylation and ubiquitination, which have been suggested to reduce or enhance IKKγ activity, respectively [16], [17].
T162 1751-2040 Sentence denotes The higher molecular weight forms of IKKγ we observed in CD40 immunoprecipitates would be consistent with the presence of post-transcriptional modifications including phosphorylation and ubiquitination, which have been suggested to reduce or enhance IKKγ activity, respectively [16], [17].
T9205 2041-2172 Sentence denotes The mechanisms by which HOIP mediates recruitment of the IKK complex to CD40 and by which HOIP is recruited to CD40 remain unclear.
T163 2041-2172 Sentence denotes The mechanisms by which HOIP mediates recruitment of the IKK complex to CD40 and by which HOIP is recruited to CD40 remain unclear.
T9206 2173-2355 Sentence denotes A previous study indicates that HOIP may mediate direct contacts with the IKK complex [16], suggesting that it functions as an adaptor for the recruitment of the IKK complex to CD40.
T164 2173-2355 Sentence denotes A previous study indicates that HOIP may mediate direct contacts with the IKK complex [16], suggesting that it functions as an adaptor for the recruitment of the IKK complex to CD40.
T9207 2356-2459 Sentence denotes However, the ubiquitin ligase activity of HOIP suggests that it is more than a simple adapter molecule.
T165 2356-2459 Sentence denotes However, the ubiquitin ligase activity of HOIP suggests that it is more than a simple adapter molecule.
T9208 2460-2711 Sentence denotes As IKKγ appears capable of binding linear polyubiquitin [18], [19], it is possible that HOIP directs formation of linear polyubiquitin chains on a CD40-associated factor, and it is these chains that serve to recruit IKKγ to the CD40 signaling complex.
T166 2460-2711 Sentence denotes As IKKγ appears capable of binding linear polyubiquitin [18], [19], it is possible that HOIP directs formation of linear polyubiquitin chains on a CD40-associated factor, and it is these chains that serve to recruit IKKγ to the CD40 signaling complex.
T9209 2712-2848 Sentence denotes The molecular interactions necessary for recruitment of HOIP itself to the CD40 signaling complex also remain to be fully characterized.
T167 2712-2848 Sentence denotes The molecular interactions necessary for recruitment of HOIP itself to the CD40 signaling complex also remain to be fully characterized.
T9210 2849-2947 Sentence denotes We previously showed that the recruitment of HOIP to the signaling complex is TRAF2-dependent [8].
T168 2849-2947 Sentence denotes We previously showed that the recruitment of HOIP to the signaling complex is TRAF2-dependent [8].
T9211 2948-3239 Sentence denotes Potentially, TRAF2 and HOIP directly interact, but it is possible that the ubiquitin ligase activity of TRAF2 [20] (or TRAF2-associated proteins, such as the cIAPs [21]) generates K63-linked polyubiquitin chains to which HOIP can bind and thus associate with the CD40 signaling complex [22].
T169 2948-3239 Sentence denotes Potentially, TRAF2 and HOIP directly interact, but it is possible that the ubiquitin ligase activity of TRAF2 [20] (or TRAF2-associated proteins, such as the cIAPs [21]) generates K63-linked polyubiquitin chains to which HOIP can bind and thus associate with the CD40 signaling complex [22].
T9212 3240-3425 Sentence denotes While our previous work indicated a potentially important link between TRAF2 and HOIP in CD40 signaling, the signals and functions tested here are dependent upon TRAF6 as well as TRAF2.
T170 3240-3425 Sentence denotes While our previous work indicated a potentially important link between TRAF2 and HOIP in CD40 signaling, the signals and functions tested here are dependent upon TRAF6 as well as TRAF2.
T9213 3426-3647 Sentence denotes In previous experiments with TRAF-deficient A20.2J cells, we found that the activation of NF-κB by CD40 could be mediated by either TRAF2 or TRAF6, while activation of JNK by CD40 was largely dependent on TRAF6 alone [8].
T171 3426-3647 Sentence denotes In previous experiments with TRAF-deficient A20.2J cells, we found that the activation of NF-κB by CD40 could be mediated by either TRAF2 or TRAF6, while activation of JNK by CD40 was largely dependent on TRAF6 alone [8].
T9214 3648-3810 Sentence denotes HOIP deficiency compromises the CD40-mediated activation of both NF-κB and JNK, indicating that signals mediated by both TRAF2 and TRAF6 likely pass through HOIP.
T172 3648-3810 Sentence denotes HOIP deficiency compromises the CD40-mediated activation of both NF-κB and JNK, indicating that signals mediated by both TRAF2 and TRAF6 likely pass through HOIP.
T9215 3811-4100 Sentence denotes Our previous work also demonstrated that the CD40-mediated activation of NF-κB and JNK, while TRAF6-dependent, was not compromised by the disruption of the binding site for TRAF6 in the cytoplasmic domain of CD40 or deletion of the receptor binding domain (the TRAF-C domain) in TRAF6 [8].
T173 3811-4100 Sentence denotes Our previous work also demonstrated that the CD40-mediated activation of NF-κB and JNK, while TRAF6-dependent, was not compromised by the disruption of the binding site for TRAF6 in the cytoplasmic domain of CD40 or deletion of the receptor binding domain (the TRAF-C domain) in TRAF6 [8].
T9216 4101-4294 Sentence denotes These observations indicate that TRAF6 need not directly bind CD40 in order to mediate certain signals, suggesting the assembly of a signaling complex not directly associated with the receptor.
T174 4101-4294 Sentence denotes These observations indicate that TRAF6 need not directly bind CD40 in order to mediate certain signals, suggesting the assembly of a signaling complex not directly associated with the receptor.
T9217 4295-4400 Sentence denotes If such a complex exists, our results indicate that the absence of HOIP compromises its function as well.
T175 4295-4400 Sentence denotes If such a complex exists, our results indicate that the absence of HOIP compromises its function as well.
T9218 4401-4725 Sentence denotes Although the experiments presented here focus on CD40, our results and those of other groups [16], [22] support the possibility that HOIP is important in many signaling pathways in which TRAF2 or TRAF6 are involved, including those associated with various members of the TNF receptor superfamily and the Toll-like receptors.
T176 4401-4725 Sentence denotes Although the experiments presented here focus on CD40, our results and those of other groups [16], [22] support the possibility that HOIP is important in many signaling pathways in which TRAF2 or TRAF6 are involved, including those associated with various members of the TNF receptor superfamily and the Toll-like receptors.
T9219 4726-5101 Sentence denotes The potential importance of HOIP in immune function and TNFR family signaling is further supported by the recent discovery that HOIP interacts with a protein known as SHARPIN (SHANK-associated RH domain interacting protein in postsynaptic density), which appears capable of working together with HOIP and HOIL to mediate the assembly of linear polyubiquitin [14], [23], [24].
T177 4726-5101 Sentence denotes The potential importance of HOIP in immune function and TNFR family signaling is further supported by the recent discovery that HOIP interacts with a protein known as SHARPIN (SHANK-associated RH domain interacting protein in postsynaptic density), which appears capable of working together with HOIP and HOIL to mediate the assembly of linear polyubiquitin [14], [23], [24].
T9220 5102-5417 Sentence denotes Interestingly, mice with a spontaneous mutation in the gene encoding SHARPIN (chronic proliferative dermatitis (cpdm) mice) exhibit chronic inflammation of the skin and internal organs, defective development of secondary lymphoid tissue, and defects in the production of switched immunoglobulin isotypes [17], [25].
T178 5102-5417 Sentence denotes Interestingly, mice with a spontaneous mutation in the gene encoding SHARPIN (chronic proliferative dermatitis (cpdm) mice) exhibit chronic inflammation of the skin and internal organs, defective development of secondary lymphoid tissue, and defects in the production of switched immunoglobulin isotypes [17], [25].
T9221 5418-5599 Sentence denotes The apparently intimate functional link between SHARPIN and HOIP strongly suggests that at least part of the cpdm phenotype stems from defects in the regulation or function of HOIP.
T179 5418-5599 Sentence denotes The apparently intimate functional link between SHARPIN and HOIP strongly suggests that at least part of the cpdm phenotype stems from defects in the regulation or function of HOIP.