Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles
Identifieur interne : 000190 ( Main/Exploration ); précédent : 000189; suivant : 000191Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles
Auteurs : Huayang Liu [États-Unis] ; Xing Tang [États-Unis] ; Arunima Srivastava [États-Unis] ; Thierry Pécot [France] ; Piotr Daniel [États-Unis] ; Benjamin Hemmelgarn [États-Unis] ; Stephan Reyes [États-Unis] ; Nicholas Fackler [États-Unis] ; Amneet Bajwa [États-Unis] ; Raleigh Kladney [États-Unis] ; Christopher Koivisto [États-Unis] ; Zhong Chen [États-Unis] ; Qianben Wang [États-Unis] ; Kun Huang [États-Unis] ; Raghu Machiraju [États-Unis] ; Maria Teresa Saenz-Robles [États-Unis] ; Paul Cantalupo [États-Unis] ; James Pipas [États-Unis] ; Gustavo Leone [États-Unis]Source :
- Nature Cell Biology [ 1465-7392 ] ; 2015-07-20.
Abstract
Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells using a murine intestinal model. We show that Myc and E2f1–3 have little impact on normal G1–S transitions. Instead, they synergistically control an S–G2 transcriptional program required for normal cell divisions and maintaining crypt–villus integrity. Surprisingly, Rb deficiency results in the Myc-dependent accumulation of E2f3 protein and chromatin repositioning of both Myc and E2f3, leading to the ‘super activation’ of a G1–S transcriptional program, ectopic S phase entry and rampant cell proliferation. These findings reveal that Rb-deficient cells hijack and redeploy Myc and E2f3 from an S–G2 program essential for normal cell cycles to a G1–S program that re-engages ectopic cell cycles, exposing an unanticipated addiction of Rb-null cells on Myc.
Url:
DOI: 10.1038/ncb3210
Affiliations:
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</org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:hal-01244839</idno><idno type="halId">hal-01244839</idno><idno type="halUri">https://hal.inria.fr/hal-01244839</idno><idno type="url">https://hal.inria.fr/hal-01244839</idno><idno type="doi">10.1038/ncb3210</idno><date when="2015-07-20">2015-07-20</date><idno type="wicri:Area/Hal/Corpus">000501</idno><idno type="wicri:Area/Hal/Curation">000501</idno><idno type="wicri:Area/Hal/Checkpoint">000151</idno><idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000151</idno><idno type="wicri:doubleKey">1465-7392:2015:Liu H:redeployment:of:myc</idno><idno type="wicri:Area/Main/Merge">000190</idno><idno type="wicri:Area/Main/Curation">000190</idno><idno type="wicri:Area/Main/Exploration">000190</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles</title><author><name sortKey="Liu, Huayang" sort="Liu, Huayang" uniqKey="Liu H" first="Huayang" last="Liu">Huayang Liu</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-411589" status="VALID"> <orgName>Comprehensive Cancer Center [Colombus]</orgName> <desc> <address> <addrLine>460 W. 10th AvenueColumbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">http://cancer.osu.edu/</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Tang, Xing" sort="Tang, Xing" uniqKey="Tang X" first="Xing" last="Tang">Xing Tang</name><affiliation wicri:level="1"><hal:affiliation type="department" xml:id="struct-187694" status="VALID"> <orgName>Department of Molecular Virology, Immunology and Medical Genetics [Colombus]</orgName> <desc> <address> <addrLine>370 W. 9th Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">http://medicine.osu.edu/mvimg/Pages/index.aspx</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> <relation active="#struct-324599" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName 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and Medical Genetics [Colombus]</orgName> <desc> <address> <addrLine>370 W. 9th Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">http://medicine.osu.edu/mvimg/Pages/index.aspx</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> <relation active="#struct-324599" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle><tutelle active="#struct-324599" type="direct"><org type="institution" xml:id="struct-324599" status="VALID"> <orgName>College of Medicine and Public Health [Colombus]</orgName> <desc> <address> 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Immunology and Medical Genetics [Colombus]</orgName> <desc> <address> <addrLine>370 W. 9th Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">http://medicine.osu.edu/mvimg/Pages/index.aspx</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> <relation active="#struct-324599" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle><tutelle active="#struct-324599" type="direct"><org type="institution" xml:id="struct-324599" status="VALID"> <orgName>College of Medicine and Public Health [Colombus]</orgName> <desc> 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type="url">http://medicine.osu.edu/mvimg/Pages/index.aspx</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> <relation active="#struct-324599" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle><tutelle active="#struct-324599" type="direct"><org type="institution" xml:id="struct-324599" status="VALID"> <orgName>College of Medicine and Public Health [Colombus]</orgName> <desc> <address> <addrLine>250 Cunz Hall1841 Neil Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">https://cph.osu.edu/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Chen, Zhong" sort="Chen, Zhong" uniqKey="Chen Z" first="Zhong" last="Chen">Zhong Chen</name><affiliation wicri:level="1"><hal:affiliation type="department" xml:id="struct-187694" status="VALID"> <orgName>Department of Molecular Virology, Immunology and Medical Genetics [Colombus]</orgName> <desc> <address> <addrLine>370 W. 9th Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">http://medicine.osu.edu/mvimg/Pages/index.aspx</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> <relation active="#struct-324599" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle><tutelle active="#struct-324599" type="direct"><org type="institution" xml:id="struct-324599" status="VALID"> <orgName>College of Medicine and Public Health [Colombus]</orgName> <desc> <address> <addrLine>250 Cunz Hall1841 Neil Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">https://cph.osu.edu/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Wang, Qianben" sort="Wang, Qianben" uniqKey="Wang Q" first="Qianben" last="Wang">Qianben Wang</name><affiliation wicri:level="1"><hal:affiliation type="department" xml:id="struct-187694" status="VALID"> <orgName>Department of Molecular Virology, Immunology and Medical Genetics [Colombus]</orgName> <desc> <address> <addrLine>370 W. 9th Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">http://medicine.osu.edu/mvimg/Pages/index.aspx</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> <relation active="#struct-324599" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle><tutelle active="#struct-324599" type="direct"><org type="institution" xml:id="struct-324599" status="VALID"> <orgName>College of Medicine and Public Health [Colombus]</orgName> <desc> <address> <addrLine>250 Cunz Hall1841 Neil Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">https://cph.osu.edu/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Huang, Kun" sort="Huang, Kun" uniqKey="Huang K" first="Kun" last="Huang">Kun Huang</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-128994" status="VALID"> <orgName>Department of Biomedical Informatics [Columbus]</orgName> <desc> <address> <country key="US"></country> </address> <ref type="url">http://medicine.osu.edu/bmi/Pages/index.aspx</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Machiraju, Raghu" sort="Machiraju, Raghu" uniqKey="Machiraju R" first="Raghu" last="Machiraju">Raghu Machiraju</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-229818" status="VALID"> <orgName>Department of Computer Science and Engineering [Colombus]</orgName> <desc> <address> <addrLine>Ohio State University 395 Dreese Laboratories 2015 Neil Avenue Columbus, OH 43210-1277</addrLine> <country key="US"></country> </address> <ref type="url">http://www.cse.ohio-state.edu/</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Saenz Robles, Maria Teresa" sort="Saenz Robles, Maria Teresa" uniqKey="Saenz Robles M" first="Maria Teresa" last="Saenz-Robles">Maria Teresa Saenz-Robles</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-92724" status="VALID"> <orgName>Department of Biological Sciences [Pittsburgh]</orgName> <desc> <address> <addrLine>4400 Fifth Avenue Pittsburgh, PA 15213</addrLine> <country key="US"></country> </address> <ref type="url">http://www.cmu.edu/bio/</ref> </desc> <listRelation> <relation active="#struct-67135" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-67135" type="direct"><org type="institution" xml:id="struct-67135" status="VALID"> <orgName>Carnegie Mellon University [Pittsburgh]</orgName> <orgName type="acronym">CMU</orgName> <desc> <address> <addrLine>5000 Forbes Ave, Pittsburgh, PA 15213</addrLine> <country key="US"></country> </address> <ref type="url">http://www.cmu.edu/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Cantalupo, Paul" sort="Cantalupo, Paul" uniqKey="Cantalupo P" first="Paul" last="Cantalupo">Paul Cantalupo</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-92724" status="VALID"> <orgName>Department of Biological Sciences [Pittsburgh]</orgName> <desc> <address> <addrLine>4400 Fifth Avenue Pittsburgh, PA 15213</addrLine> <country key="US"></country> </address> <ref type="url">http://www.cmu.edu/bio/</ref> </desc> <listRelation> <relation active="#struct-67135" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-67135" type="direct"><org type="institution" xml:id="struct-67135" status="VALID"> <orgName>Carnegie Mellon University [Pittsburgh]</orgName> <orgName type="acronym">CMU</orgName> <desc> <address> <addrLine>5000 Forbes Ave, Pittsburgh, PA 15213</addrLine> <country key="US"></country> </address> <ref type="url">http://www.cmu.edu/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Pipas, James" sort="Pipas, James" uniqKey="Pipas J" first="James" last="Pipas">James Pipas</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-92724" status="VALID"> <orgName>Department of Biological Sciences [Pittsburgh]</orgName> <desc> <address> <addrLine>4400 Fifth Avenue Pittsburgh, PA 15213</addrLine> <country key="US"></country> </address> <ref type="url">http://www.cmu.edu/bio/</ref> </desc> <listRelation> <relation active="#struct-67135" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-67135" type="direct"><org type="institution" xml:id="struct-67135" status="VALID"> <orgName>Carnegie Mellon University [Pittsburgh]</orgName> <orgName type="acronym">CMU</orgName> <desc> <address> <addrLine>5000 Forbes Ave, Pittsburgh, PA 15213</addrLine> <country key="US"></country> </address> <ref type="url">http://www.cmu.edu/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Leone, Gustavo" sort="Leone, Gustavo" uniqKey="Leone G" first="Gustavo" last="Leone">Gustavo Leone</name><affiliation wicri:level="1"><hal:affiliation type="department" xml:id="struct-187694" status="VALID"> <orgName>Department of Molecular Virology, Immunology and Medical Genetics [Colombus]</orgName> <desc> <address> <addrLine>370 W. 9th Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">http://medicine.osu.edu/mvimg/Pages/index.aspx</ref> </desc> <listRelation> <relation active="#struct-86555" type="direct"></relation> <relation active="#struct-324599" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-86555" type="direct"><org type="institution" xml:id="struct-86555" status="VALID"><orgName>Ohio State University [Columbus]</orgName><orgName type="acronym">OSU</orgName><desc><address><addrLine>Ohio State University Enarson Hall 154 W 12th Avenue Columbus, Ohio 43210</addrLine><country key="US"></country></address><ref type="url">http://www.osu.edu/</ref></desc></org></tutelle><tutelle active="#struct-324599" type="direct"><org type="institution" xml:id="struct-324599" status="VALID"> <orgName>College of Medicine and Public Health [Colombus]</orgName> <desc> <address> <addrLine>250 Cunz Hall1841 Neil Ave.Columbus, OH 43210</addrLine> <country key="US"></country> </address> <ref type="url">https://cph.osu.edu/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author></analytic><idno type="DOI">10.1038/ncb3210</idno><series><title level="j">Nature Cell Biology</title><idno type="ISSN">1465-7392</idno><imprint><date type="datePub">2015-07-20</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells using a murine intestinal model. We show that Myc and E2f1–3 have little impact on normal G1–S transitions. Instead, they synergistically control an S–G2 transcriptional program required for normal cell divisions and maintaining crypt–villus integrity. Surprisingly, Rb deficiency results in the Myc-dependent accumulation of E2f3 protein and chromatin repositioning of both Myc and E2f3, leading to the ‘super activation’ of a G1–S transcriptional program, ectopic S phase entry and rampant cell proliferation. These findings reveal that Rb-deficient cells hijack and redeploy Myc and E2f3 from an S–G2 program essential for normal cell cycles to a G1–S program that re-engages ectopic cell cycles, exposing an unanticipated addiction of Rb-null cells on Myc.</div></front></TEI><affiliations><list><country><li>France</li><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Liu, Huayang" sort="Liu, Huayang" uniqKey="Liu H" first="Huayang" last="Liu">Huayang Liu</name></noRegion><name sortKey="Bajwa, Amneet" sort="Bajwa, Amneet" uniqKey="Bajwa A" first="Amneet" last="Bajwa">Amneet Bajwa</name><name sortKey="Cantalupo, Paul" sort="Cantalupo, Paul" uniqKey="Cantalupo P" first="Paul" last="Cantalupo">Paul Cantalupo</name><name sortKey="Chen, Zhong" sort="Chen, Zhong" uniqKey="Chen Z" first="Zhong" last="Chen">Zhong Chen</name><name sortKey="Daniel, Piotr" sort="Daniel, Piotr" uniqKey="Daniel P" first="Piotr" last="Daniel">Piotr Daniel</name><name sortKey="Fackler, Nicholas" sort="Fackler, Nicholas" uniqKey="Fackler N" first="Nicholas" last="Fackler">Nicholas Fackler</name><name sortKey="Hemmelgarn, Benjamin" sort="Hemmelgarn, Benjamin" uniqKey="Hemmelgarn B" first="Benjamin" last="Hemmelgarn">Benjamin Hemmelgarn</name><name sortKey="Huang, Kun" sort="Huang, Kun" uniqKey="Huang K" first="Kun" last="Huang">Kun Huang</name><name sortKey="Kladney, Raleigh" sort="Kladney, Raleigh" uniqKey="Kladney R" first="Raleigh" last="Kladney">Raleigh Kladney</name><name sortKey="Koivisto, Christopher" sort="Koivisto, Christopher" uniqKey="Koivisto C" first="Christopher" last="Koivisto">Christopher Koivisto</name><name sortKey="Leone, Gustavo" sort="Leone, Gustavo" uniqKey="Leone G" first="Gustavo" last="Leone">Gustavo Leone</name><name sortKey="Machiraju, Raghu" sort="Machiraju, Raghu" uniqKey="Machiraju R" first="Raghu" last="Machiraju">Raghu Machiraju</name><name sortKey="Pipas, James" sort="Pipas, James" uniqKey="Pipas J" first="James" last="Pipas">James Pipas</name><name sortKey="Reyes, Stephan" sort="Reyes, Stephan" uniqKey="Reyes S" first="Stephan" last="Reyes">Stephan Reyes</name><name sortKey="Saenz Robles, Maria Teresa" sort="Saenz Robles, Maria Teresa" uniqKey="Saenz Robles M" first="Maria Teresa" last="Saenz-Robles">Maria Teresa Saenz-Robles</name><name sortKey="Srivastava, Arunima" sort="Srivastava, Arunima" uniqKey="Srivastava A" first="Arunima" last="Srivastava">Arunima Srivastava</name><name sortKey="Tang, Xing" sort="Tang, Xing" uniqKey="Tang X" first="Xing" last="Tang">Xing Tang</name><name sortKey="Wang, Qianben" sort="Wang, Qianben" uniqKey="Wang Q" first="Qianben" last="Wang">Qianben Wang</name></country><country name="France"><noRegion><name sortKey="Pecot, Thierry" sort="Pecot, Thierry" uniqKey="Pecot T" first="Thierry" last="Pécot">Thierry Pécot</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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