title: Murine Schnurri-2 controls natural killer cell function and lymphoma development.
abstract: Schnurri (Shn)-2 is a large zinc finger-containing protein implicated in cell growth, signal transduction and lymphocyte development. Here, we report that Shn-2-deficient (Shn-2(-/-)) mice develop CD3-positive lymphoma spontaneously. In Shn-2(-/-) mice, we observed decreased cytotoxicity of natural killer (NK) cells accompanied by decreased expression of perforin and granzyme-B. In addition, phosphorylation of signal transducer and activator of transcription (STAT) 5 was reduced in Shn-2(-/-) NK cells, while phosphorylation of STAT3 and protein expression of nuclear factor-κB p65 subunit were enhanced in Shn-2(-/-) NK cells. Moreover, cell-surface expression of activation molecules such as CD27, CD69 and CD122 were decreased on Shn-2(-/-) NK cells. Thus, Shn-2 is considered to play an important role in the activation and function of NK cells and the development of T cell lymphoma in vivo.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yamashita
authors.forename: Chiaki
authors.initials: C
authors.lastname: Iwamura
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Mitsumori
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sasaki
authors.forename: Munehisa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kaneko
authors.forename: Asami
authors.initials: A
authors.lastname: Hanazawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.forename: Damon
authors.initials: D
authors.lastname: Tumes
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053804:Granzymes / Q000032:analysis; D007113:Immunity, Innate; D007157:Immunologic Surveillance; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D008168:Lung / Q000473:pathology; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054353:Perforin / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology
chemical_list: D017252:CD3 Complex; D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse; D007376:Interleukin-2; D009363:Neoplasm Proteins; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse