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Article: HES1 opposes a PTEN-dependent check on survival, differentiation, and proliferation of TCRβ-selected mouse thymocytes

TitleHES1 opposes a PTEN-dependent check on survival, differentiation, and proliferation of TCRβ-selected mouse thymocytes
Authors
Issue Date2012
Citation
Blood, 2012, v. 120, n. 7, p. 1439-1448 How to Cite?
AbstractThe developmental progression of immature thymocytes requires cooperative input from several pathways, with Notch signals playing an indispensable role at the T-cell receptor (TCR)-β selection checkpoint. Notch signals affect the activation of the PI3K/Akt pathway, which is required for pTα/TCRβ (pre-TCR)-induced survival, differentiation, and proliferation of developing αβ-lineage thymocytes. However, the molecular players responsible for the interaction between the Notch and PI3K pathways at this critical developmental stage are unknown. Here, we show that Notch induction of Hes1 is necessary to repress the PI3K/Akt pathway inhibitor, PTEN (phosphatase and tensin homolog), which in turn facilitates pre-TCR-induced differentiation. In support of this mechanism, deletion or down-regulation of Pten overcomes the Notch signaling requirement for survival and differentiation during β-selection. In addition, c-Myc is a critical target of Notch at this stage, as c-Myc expression overcomes the Notch signaling requirement for proliferation during β-selection. Collectively, our results point to HES1, via repression of PTEN, and c-Myc as critical mediators of Notch function at the β-selection checkpoint. © 2012 by The American Society of Hematology.
Persistent Identifierhttp://hdl.handle.net/10722/292719
ISSN
2023 Impact Factor: 21.0
2023 SCImago Journal Rankings: 5.272
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, Gladys W.-
dc.contributor.authorKnowles, Gisele C.-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorFerrando, Adolfo A.-
dc.contributor.authorZúñiga-Pflücker, Juan Carlos-
dc.date.accessioned2020-11-17T14:57:04Z-
dc.date.available2020-11-17T14:57:04Z-
dc.date.issued2012-
dc.identifier.citationBlood, 2012, v. 120, n. 7, p. 1439-1448-
dc.identifier.issn0006-4971-
dc.identifier.urihttp://hdl.handle.net/10722/292719-
dc.description.abstractThe developmental progression of immature thymocytes requires cooperative input from several pathways, with Notch signals playing an indispensable role at the T-cell receptor (TCR)-β selection checkpoint. Notch signals affect the activation of the PI3K/Akt pathway, which is required for pTα/TCRβ (pre-TCR)-induced survival, differentiation, and proliferation of developing αβ-lineage thymocytes. However, the molecular players responsible for the interaction between the Notch and PI3K pathways at this critical developmental stage are unknown. Here, we show that Notch induction of Hes1 is necessary to repress the PI3K/Akt pathway inhibitor, PTEN (phosphatase and tensin homolog), which in turn facilitates pre-TCR-induced differentiation. In support of this mechanism, deletion or down-regulation of Pten overcomes the Notch signaling requirement for survival and differentiation during β-selection. In addition, c-Myc is a critical target of Notch at this stage, as c-Myc expression overcomes the Notch signaling requirement for proliferation during β-selection. Collectively, our results point to HES1, via repression of PTEN, and c-Myc as critical mediators of Notch function at the β-selection checkpoint. © 2012 by The American Society of Hematology.-
dc.languageeng-
dc.relation.ispartofBlood-
dc.titleHES1 opposes a PTEN-dependent check on survival, differentiation, and proliferation of TCRβ-selected mouse thymocytes-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1182/blood-2011-12-395319-
dc.identifier.pmid22649105-
dc.identifier.pmcidPMC3423782-
dc.identifier.scopuseid_2-s2.0-84865160657-
dc.identifier.volume120-
dc.identifier.issue7-
dc.identifier.spage1439-
dc.identifier.epage1448-
dc.identifier.eissn1528-0020-
dc.identifier.isiWOS:000309001900016-
dc.identifier.f1000717956883-
dc.identifier.issnl0006-4971-

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