Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter
One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the...
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| Veröffentlicht in: | Cell death and differentiation 2006-09, Vol.13 (9), p.1495-1505 |
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| creator | Jang, J Choi, Y I Choi, J Lee, K Y Chung, H Jeon, S H Seong, R H |
| description | One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation. |
| doi_str_mv | 10.1038/sj.cdd.4401827 |
| format | Article |
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We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation.</description><identifier>ISSN: 1350-9047</identifier><identifier>EISSN: 1476-5403</identifier><identifier>DOI: 10.1038/sj.cdd.4401827</identifier><identifier>PMID: 16341126</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Antigens ; Apoptosis ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Basic-Leucine Zipper Transcription Factors - metabolism ; Biochemistry ; CD4 antigen ; CD8 antigen ; Cell Biology ; Cell Cycle Analysis ; Cell death ; Cell Differentiation ; Cell Line ; Cell Survival - drug effects ; DNA-Binding Proteins - metabolism ; E1A-Associated p300 Protein - metabolism ; Glucocorticoids ; Glucocorticoids - pharmacology ; HEB protein ; Humans ; Immunoglobulin J Recombination Signal Sequence-Binding Protein - genetics ; Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism ; Life Sciences ; Maturation ; Mice ; Mice, Inbred C57BL ; Mutation ; Notch1 protein ; Oncogene Proteins, Fusion - metabolism ; original-paper ; Promoter Regions, Genetic ; Protein Binding ; Receptor, Notch1 - physiology ; Repressor Proteins - genetics ; Signal Transduction ; Stem Cells ; T-Lymphocytes - cytology ; T-Lymphocytes - drug effects ; T-Lymphocytes - physiology ; Thymocytes ; Trans-Activators - genetics ; Transcription activation ; Transcriptional Activation</subject><ispartof>Cell death and differentiation, 2006-09, Vol.13 (9), p.1495-1505</ispartof><rights>Springer Nature Limited 2006</rights><rights>Copyright Nature Publishing Group Sep 2006</rights><rights>Nature Publishing Group 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-6922159f018296e7d0dfd6eedf52273608c4a911e79a8d344849d0cb8dfa32943</citedby><cites>FETCH-LOGICAL-c428t-6922159f018296e7d0dfd6eedf52273608c4a911e79a8d344849d0cb8dfa32943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.cdd.4401827$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.cdd.4401827$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16341126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jang, J</creatorcontrib><creatorcontrib>Choi, Y I</creatorcontrib><creatorcontrib>Choi, J</creatorcontrib><creatorcontrib>Lee, K Y</creatorcontrib><creatorcontrib>Chung, H</creatorcontrib><creatorcontrib>Jeon, S H</creatorcontrib><creatorcontrib>Seong, R H</creatorcontrib><title>Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter</title><title>Cell death and differentiation</title><addtitle>Cell Death Differ</addtitle><addtitle>Cell Death Differ</addtitle><description>One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation.</description><subject>Animals</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Basic-Leucine Zipper Transcription Factors - metabolism</subject><subject>Biochemistry</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell Biology</subject><subject>Cell Cycle Analysis</subject><subject>Cell death</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>E1A-Associated p300 Protein - metabolism</subject><subject>Glucocorticoids</subject><subject>Glucocorticoids - pharmacology</subject><subject>HEB protein</subject><subject>Humans</subject><subject>Immunoglobulin J Recombination Signal Sequence-Binding Protein - genetics</subject><subject>Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism</subject><subject>Life Sciences</subject><subject>Maturation</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mutation</subject><subject>Notch1 protein</subject><subject>Oncogene Proteins, Fusion - metabolism</subject><subject>original-paper</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Receptor, Notch1 - physiology</subject><subject>Repressor Proteins - genetics</subject><subject>Signal Transduction</subject><subject>Stem Cells</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - physiology</subject><subject>Thymocytes</subject><subject>Trans-Activators - genetics</subject><subject>Transcription activation</subject><subject>Transcriptional Activation</subject><issn>1350-9047</issn><issn>1476-5403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kV2L1DAUhoso7rp666UEBe86m5NkkuZSRh2FRcGP65BJTmc6tk1NUnB-gX_blBlYEPYqgffJc054q-ol0BVQ3tym48p5vxKCQsPUo-oahJL1WlD-uNz5mtaaCnVVPUvpSCmVSsun1RVILgCYvK7-fgnZHYC4MLYYE8mH0xDcKWMilkRMXcp2dEhyINtN3Y1-duiJncKUQwkLH8O8P5D32Gf8A2R3Irs-uF_duC8ZFoWLc5cHHDMJLZk4pYtrib5_23IyxTCEjPF59aS1fcIXl_Om-vnxw4_Np_ru6_bz5t1d7QRrci01Y7DW7fJbLVF56lsvEX27ZkxxSRsnrAZApW3juRCN0J66XeNby5kW_KZ6e_aWwb9nTNkMXXLY93bEMCcjm2JpNBTwzX_gMcxxLLsZpgCopqAW6vWDFCjFgAEv0OoMuRhSitiaKXaDjScD1CwtmnQ0pUVzabE8eHWxzrsB_T1-qa0At2cglWjcY7wf-4DyH2Ncp5g</recordid><startdate>20060901</startdate><enddate>20060901</enddate><creator>Jang, J</creator><creator>Choi, Y I</creator><creator>Choi, J</creator><creator>Lee, K Y</creator><creator>Chung, H</creator><creator>Jeon, S H</creator><creator>Seong, R H</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20060901</creationdate><title>Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter</title><author>Jang, J ; Choi, Y I ; Choi, J ; Lee, K Y ; Chung, H ; Jeon, S H ; Seong, R H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-6922159f018296e7d0dfd6eedf52273608c4a911e79a8d344849d0cb8dfa32943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antigens</topic><topic>Apoptosis</topic><topic>Basic Helix-Loop-Helix Transcription Factors - 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Academic</collection><jtitle>Cell death and differentiation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jang, J</au><au>Choi, Y I</au><au>Choi, J</au><au>Lee, K Y</au><au>Chung, H</au><au>Jeon, S H</au><au>Seong, R H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter</atitle><jtitle>Cell death and differentiation</jtitle><stitle>Cell Death Differ</stitle><addtitle>Cell Death Differ</addtitle><date>2006-09-01</date><risdate>2006</risdate><volume>13</volume><issue>9</issue><spage>1495</spage><epage>1505</epage><pages>1495-1505</pages><issn>1350-9047</issn><eissn>1476-5403</eissn><abstract>One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16341126</pmid><doi>10.1038/sj.cdd.4401827</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens Apoptosis Basic Helix-Loop-Helix Transcription Factors - metabolism Basic-Leucine Zipper Transcription Factors - metabolism Biochemistry CD4 antigen CD8 antigen Cell Biology Cell Cycle Analysis Cell death Cell Differentiation Cell Line Cell Survival - drug effects DNA-Binding Proteins - metabolism E1A-Associated p300 Protein - metabolism Glucocorticoids Glucocorticoids - pharmacology HEB protein Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein - genetics Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism Life Sciences Maturation Mice Mice, Inbred C57BL Mutation Notch1 protein Oncogene Proteins, Fusion - metabolism original-paper Promoter Regions, Genetic Protein Binding Receptor, Notch1 - physiology Repressor Proteins - genetics Signal Transduction Stem Cells T-Lymphocytes - cytology T-Lymphocytes - drug effects T-Lymphocytes - physiology Thymocytes Trans-Activators - genetics Transcription activation Transcriptional Activation |
| title | Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter |
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