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dc.contributor.authorMartín, Ren
dc.contributor.authorPortantier, Men
dc.contributor.authorChica, Nen
dc.contributor.authorNyquist-Andersen, Men
dc.contributor.authorMata, Juanen
dc.contributor.authorLopez-Aviles, Sen
dc.date.accessioned2017-02-13T10:55:09Z
dc.date.available2017-02-13T10:55:09Z
dc.date.issued2017-01-23en
dc.identifier.issn0960-9822
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262469
dc.description.abstractExtracellular cues regulate cell fate, and this is mainly achieved through the engagement of specific transcriptional programs. The TORC1 and TORC2 complexes mediate the integration of nutritional cues to cellular behavior, but their interplay is poorly understood. Here, we use fission yeast to investigate how phosphatase activity participates in this interplay during the switch from proliferation to sexual differentiation. We find that loss of PP2A-B55$^{Pab1}$ enhances the expression of differentiation-specific genes and leads to premature conjugation. $\textit{pab1}$ deletion brings about a transcriptional profile similar to TORC1 inactivation, and deletion of $\textit{pab1}$ overcomes the repression of differentiation genes in cells overexpressing TORC1. Importantly, we show that this effect is mediated by an increased TORC2-AKT (Gad8) signaling. Under nutrient-rich conditions, PP2A-B55$^{Pab1}$ dephosphorylates Gad8 Ser546, repressing its activity. Conversely, TORC1 inactivation upon starvation leads to the inactivation of PP2A-B55$^{Pab1}$ through the Greatwall-Endosulfin pathway. This results in the activation of Gad8 and the commitment to differentiation. Thus, PP2A-B55$^{Pab1}$ enables a crosstalk between the two TOR complexes that controls cell-fate decisions in response to nutrient availability.
dc.description.sponsorshipWe thank Dominique Helmlinger and Sergio Moreno for sharing unpublished results and strains, and for stimulating discussion. We thank Janni Petersen, Ronit Weisman, Kazuhiro Shiozaki, Mitsuhiro Yanagida, and Hisao Masukata for strains, constructs, and antibodies. We thank Toni Hurtado and Beata Grallert for critical reading of the manuscript. This work was supported by NFR FRIMEDBIO grant 214049. M.P. is the recipient of a Kreftforeningen postdoctoral fellowship (grant 5843744). N.C. has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement 609020 - Scientia Fellows. J.M. was supported by BBSRC research grants BB/N007697/1 and BB/M021483/1.
dc.languageengen
dc.language.isoenen
dc.publisherElsevier (Cell Press)
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectsexual differentiationen
dc.subjectnitrogen starvationen
dc.subjectTORC1en
dc.subjectTORC2en
dc.subjectGad8en
dc.subjectPP2Aen
dc.subjectB55en
dc.subjectS. pombeen
dc.titleA PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeasten
dc.typeArticle
prism.endingPage188
prism.issueIdentifier2en
prism.publicationDate2017en
prism.publicationNameCurrent Biologyen
prism.startingPage175
prism.volume27en
dc.identifier.doi10.17863/CAM.7731
dcterms.dateAccepted2016-11-14en
rioxxterms.versionofrecord10.1016/j.cub.2016.11.037en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-01-23en
dc.contributor.orcidMata, Juan [0000-0002-5514-3653]
dc.identifier.eissn1879-0445
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/M021483/1)
pubs.funder-project-idBBSRC (BB/N07697/1)
cam.issuedOnline2016-12-29en
cam.orpheus.successThu Jan 30 12:56:47 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International