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dc.contributor.authorJacobsen, Nicole L
dc.contributor.authorPontifex, Tasha K
dc.contributor.authorLanglais, Paul R
dc.contributor.authorBurt, Janis M
dc.date.accessioned2019-07-08T17:20:15Z
dc.date.available2019-07-08T17:20:15Z
dc.date.issued2019-02-06
dc.identifier.citationJacobsen NL, Pontifex TK, Langlais PR, Burt JM. Phosphorylation-Dependent Intra-Domain Interaction of the Cx37 Carboxyl-Terminus Controls Cell Survival. Cancers. 2019; 11(2):188.en_US
dc.identifier.issn2072-6694
dc.identifier.pmid30736283
dc.identifier.doi10.3390/cancers11020188
dc.identifier.urihttp://hdl.handle.net/10150/633329
dc.description.abstractDifferential phosphorylation of the carboxyl-terminus of connexin 37 (Cx37-CT) regulates phenotypic switching between cell growth phenotypes (cell death, cell cycle arrest, proliferation). The specific phosphorylation events in the Cx37-CT that are necessary for these growth regulatory effects are currently unknown. Through the combined use of deletion and site specific (de)phospho-mimetic Cx37-CT mutants, our data suggest a phosphorylation-dependent interaction between the mid-tail (aa 273-317) and end-tail (aa 318-333) portions of the Cx37-CT that regulates cell survival. As detected by mass spectrometry, Cx37 was phosphorylated at serines 275, 321, and 328; phosphomimetic mutations of these sites resulted in cell death when expressed in rat insulinoma cells. Alanine substitution at S328, but not at S275 or S321, also triggered cell death. Cx37-S275D uniquely induced the death of only low density, non-contact forming cells, but neither hemichannel open probability nor channel conductance distinguished death-inducing mutants. As channel function is necessary for cell death, together the data suggest that the phosphorylation state of the Cx37-CT controls an intra-domain interaction within the CT that modifies channel function and induces cell death.en_US
dc.description.sponsorshipNational Institutes of Health [HL056732, HL131712, DK098493, HL007249]; American Heart Association [16PRE2750011]en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.relation.urlhttps://www.mdpi.com/2072-6694/11/2/188en_US
dc.rights© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectcell cycleen_US
dc.subjectcell deathen_US
dc.subjectconnexinen_US
dc.subjectgap junctionen_US
dc.subjectgatingen_US
dc.subjectphosphorylationen_US
dc.titlePhosphorylation-Dependent Intra-Domain Interaction of the Cx37 Carboxyl-Terminus Controls Cell Survivalen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Physiolen_US
dc.contributor.departmentUniv Arizona, Dept Meden_US
dc.identifier.journalCANCERSen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleCancers
refterms.dateFOA2019-07-08T17:20:15Z


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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Except where otherwise noted, this item's license is described as © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.