title: Pontin is required for pre-TCR signaling at the β-selection checkpoint in T cell development.
abstract: Pontin is a chromatin remodeling factor that possesses both ATPase and DNA helicase activities. Based on high expression in lymphoid tissues, we examined whether Pontin has a T cell-specific function. We generated Pontin(f/f);Lck-Cre mice, in which Pontin can be conditionally deleted in T cells and then explored T cell-specific function of Pontin in vivo. Here, we show that specific abrogation of Pontin expression in T cells almost completely blocked development of αβ T cells at the β-selection checkpoint by inducing cell apoptosis indicating that Pontin is essential for early T cell development. Pontin-deficient thymocytes show a comparable expression level of T cell receptor (TCR)β chain, but have enhanced activation of p53 and Notch signaling compared to wild-type thymocytes. Intriguingly, the developmental block of αβ T cells can be partially rescued by loss of p53. Together, our data demonstrate a novel role of Pontin as a crucial regulator in pre-TCR signaling during T cell development.
authors.affiliation: Creative Research Initiative Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Boo
authors.affiliation: Creative Research Initiative Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea. Electronic address: sbaek@snu.ac.kr.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Division of Convergence Technology, National Cancer Center, Gyeonggi-do 410-769, South Korea. Electronic address: ho25lee@ncc.re.kr.
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation / Q000276:immunology; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D011948:Receptors, Antigen, T-Cell; D016159:Tumor Suppressor Protein p53; C525849:TIP48 protein, mouse; D004265:DNA Helicases
keywords: Notch; Pontin; T cell development; p53; β-Selection checkpoint