title: The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage fate by inducing the SOCS suppressors of cytokine signaling.
abstract: Lineage fate in the thymus is determined by mutually exclusive expression of the transcription factors ThPOK and Runx3, with ThPOK imposing the CD4(+) lineage fate and Runx3 promoting the CD8(+) lineage fate. While it is known that cytokine signals induce thymocytes to express Runx3, it is not known how ThPOK prevents thymocytes from expressing Runx3 and adopting the CD8(+) lineage fate, nor is it understood why ThPOK itself imposes the CD4(+) lineage fate on thymocytes. We now report that genes encoding members of the SOCS (suppressor of cytokine signaling) family are critical targets of ThPOK and that their induction by ThPOK represses Runx3 expression and promotes the CD4(+) lineage fate. Thus, induction of SOCS-encoding genes is the main mechanism by which ThPOK imposes the CD4(+) lineage fate in the thymus.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Megan A
authors.initials: MA
authors.lastname: Luckey
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Motoko Y
authors.initials: MY
authors.lastname: Kimura
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Waickman
authors.affiliation: Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Alfred
authors.initials: A
authors.lastname: Singer
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D019070:Cell Lineage; D050677:Core Binding Factor Alpha 3 Subunit / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; C493730:Runx3 protein, mouse; C497211:Zbtb7b protein, mouse