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dc.contributor.authorTan, Justin L.
dc.contributor.authorFogley, Rachel D.
dc.contributor.authorFlynn, Ryan A.
dc.contributor.authorAblain, Julien
dc.contributor.authorYang, Song
dc.contributor.authorDo, Brian T.
dc.contributor.authorLaga, Alvaro C.
dc.contributor.authorFujinaga, Koh
dc.contributor.authorSantoriello, Cristina
dc.contributor.authorGreer, Celeste B.
dc.contributor.authorKim, Yoon Jung
dc.contributor.authorClohessy, John G.
dc.contributor.authorBothmer, Anne
dc.contributor.authorPandell, Nicole
dc.contributor.authorAvagyan, Serine
dc.contributor.authorBrogie, John E.
dc.contributor.authorvan Rooijen, Ellen
dc.contributor.authorHagedorn, Elliott J.
dc.contributor.authorShyh-Chang, Ng
dc.contributor.authorWhite, Richard M.
dc.contributor.authorPrice, David H.
dc.contributor.authorPandolfi, Pier Paolo
dc.contributor.authorPeterlin, B. Matija
dc.contributor.authorZhou, Yi
dc.contributor.authorKim, Tae Hoon
dc.contributor.authorAsara, John M.
dc.contributor.authorChang, Howard Y.
dc.contributor.authorZon, Leonard I.
dc.contributor.authorSaint-André, Violaine
dc.contributor.authorFan, Zi Peng
dc.contributor.authorYoung, Richard A
dc.date.accessioned2018-07-13T19:01:05Z
dc.date.available2018-07-13T19:01:05Z
dc.date.issued2016-04
dc.date.submitted2016-02
dc.identifier.issn1097-2765
dc.identifier.issn1097-4164
dc.identifier.urihttp://hdl.handle.net/1721.1/116990
dc.description.abstractStudying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma.en_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/J.MOLCEL.2016.03.013en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleStress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanomaen_US
dc.typeArticleen_US
dc.identifier.citationTan, Justin L. et al. “Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.” Molecular Cell 62, 1 (April 2016): 34–46 © 2016 Elsevier Incen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorSaint-André, Violaine
dc.contributor.mitauthorFan, Zi Peng
dc.contributor.mitauthorYoung, Richard A
dc.relation.journalMolecular Cellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-07-13T17:30:01Z
dspace.orderedauthorsTan, Justin L.; Fogley, Rachel D.; Flynn, Ryan A.; Ablain, Julien; Yang, Song; Saint-André, Violaine; Fan, Zi Peng; Do, Brian T.; Laga, Alvaro C.; Fujinaga, Koh; Santoriello, Cristina; Greer, Celeste B.; Kim, Yoon Jung; Clohessy, John G.; Bothmer, Anne; Pandell, Nicole; Avagyan, Serine; Brogie, John E.; van Rooijen, Ellen; Hagedorn, Elliott J.; Shyh-Chang, Ng; White, Richard M.; Price, David H.; Pandolfi, Pier Paolo; Peterlin, B. Matija; Zhou, Yi; Kim, Tae Hoon; Asara, John M.; Chang, Howard Y.; Young, Richard A.; Zon, Leonard I.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-8855-8647
mit.licensePUBLISHER_CCen_US


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