Evolution of TNF-Induced Apoptosis Reveals 550 My of Functional Conservation

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dc.contributor.authorQuistad, Steven D
dc.contributor.authorBarott, Katie
dc.contributor.authorBarott, Katie
dc.contributor.authorSmurthwaite, Cameron A
dc.contributor.authorHilton, Brett J
dc.contributor.authorGrasis, Juris A
dc.contributor.authorWolkowicz, Roland
dc.contributor.authorRohwer, Forest
dc.date2023-05-17T18:40:10.000
dc.date.accessioned2023-05-22T12:36:28Z
dc.date.available2023-05-22T12:36:28Z
dc.date.issued2014-01-01
dc.date.submitted2017-09-28T11:49:54-07:00
dc.description.abstractThe Precambrian explosion led to the rapid appearance of most major animal phyla alive today. It has been argued that the complexity of life has steadily increased since that event. Here we challenge this hypothesis through the characterization of apoptosis in reef-building corals, representatives of some of the earliest animals. Bioinformatic analysis reveals that all of the major components of the death receptor pathway are present in coral with high-predicted structural conservation with Homo sapiens. The TNF receptor-ligand superfamilies (TNFRSF/TNFSF) are central mediators of the death receptor pathway, and the predicted proteome of Acropora digitifera contains more putative coral TNFRSF members than any organism described thus far, including humans. This high abundance of TNFRSF members, as well as the predicted structural conservation of other death receptor signaling proteins, led us to wonder what would happen if corals were exposed to a member of the human TNFSF (HuTNFα). HuTNFα was found to bind directly to coral cells, increase caspase activity, cause apoptotic blebbing and cell death, and finally induce coral bleaching. Next, immortalized human T cells (Jurkats) expressing a functional death receptor pathway (WT) and a corresponding Fas-associated death domain protein (FADD) KO cell line were exposed to a coral TNFSF member (AdTNF1) identified and purified here. AdTNF1 treatment resulted in significantly higher cell death (P < 0.0001) in WT Jurkats compared with the corresponding FADD KO, demonstrating that coral AdTNF1 activates the H. sapiens death receptor pathway. Taken together, these data show remarkable conservation of the TNF-induced apoptotic response representing 550 My of functional conservation.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/5547
dc.legacy.articleid1064
dc.legacy.fields10.1073/pnas.1405912111
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1064&amp;context=biology_papers&amp;unstamped=1
dc.rights<p>Originally published in PNAS © 2014 National Academy of Sciences.</p>
dc.source.beginpage9567
dc.source.endpage9572
dc.source.issue63
dc.source.issue26
dc.source.journalDepartmental Papers (Biology)
dc.source.journaltitlePNAS (Proceedings of the National Academy of Sciences)
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume111
dc.subject.otherevolution immunity
dc.subject.othercytokines
dc.subject.otherCnidarians
dc.subject.otherclimate change
dc.subject.otherinvertebrate
dc.subject.otherBiology
dc.subject.otherEcology and Evolutionary Biology
dc.subject.otherMarine Biology
dc.subject.otherMicrobiology
dc.titleEvolution of TNF-Induced Apoptosis Reveals 550 My of Functional Conservation
dc.typeReport
digcom.contributor.authorQuistad, Steven D
digcom.contributor.authorStotland, Aleksandr
digcom.contributor.authorisAuthorOfPublication|email:kbarott@sas.upenn.edu|institution:University of Pennsylvania|Barott, Katie
digcom.contributor.authorSmurthwaite, Cameron A
digcom.contributor.authorHilton, Brett J
digcom.contributor.authorGrasis, Juris A
digcom.contributor.authorWolkowicz, Roland
digcom.contributor.authorRohwer, Forest
digcom.identifierbiology_papers/63
digcom.identifier.contextkey10829368
digcom.identifier.submissionpathbiology_papers/63
digcom.typereport
dspace.entity.typePublication
relation.isAuthorOfPublicationffa56f10-f380-414f-b6b1-bf095362a24b
relation.isAuthorOfPublicationffa56f10-f380-414f-b6b1-bf095362a24b
relation.isAuthorOfPublication.latestForDiscoveryffa56f10-f380-414f-b6b1-bf095362a24b
upenn.schoolDepartmentCenterDepartmental Papers (Biology)
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