Your browser doesn't support javascript.
loading
EBF1-JAK2 inhibits the PAX5 function through physical interaction with PAX5 and kinase activity.
Kojima, Yukino; Kawashima, Fumika; Yasuda, Takahiko; Odaira, Koya; Inagaki, Yuichiro; Yamada, Chiharu; Muraki, Ami; Noura, Mina; Okamoto, Shuichi; Tamura, Shogo; Iwamoto, Eisuke; Sanada, Masashi; Matsumura, Itaru; Miyazaki, Yasushi; Kojima, Tetsuhito; Kiyoi, Hitoshi; Tsuzuki, Shinobu; Hayakawa, Fumihiko.
Afiliación
  • Kojima Y; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Kawashima F; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Yasuda T; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
  • Odaira K; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Inagaki Y; Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
  • Yamada C; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Muraki A; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Noura M; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Okamoto S; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Tamura S; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Iwamoto E; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
  • Sanada M; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
  • Matsumura I; Department of Hematology and Rheumatology, Kindai University School of Medicine, Osaka, Japan.
  • Miyazaki Y; Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
  • Kojima T; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-0047, Japan.
  • Kiyoi H; Aichi Health Promotion Foundation, Nagoya, Japan.
  • Tsuzuki S; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Hayakawa F; Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan.
Int J Hematol ; 118(1): 65-74, 2023 Jul.
Article en En | MEDLINE | ID: mdl-37149540
Gene aberrations of B-cell regulators and growth signal components such as the JAK-STAT pathway are frequently found in B-cell acute lymphoblastic leukemia (B-ALL). EBF1 is a B-cell regulator that regulates the expression of PAX5 and co-operates with PAX5 to regulate B-cell differentiation. Here, we analyzed the function of the fusion protein of EBF1 and JAK2, EBF1-JAK2 (E-J). E-J caused constitutive activation of JAK-STAT and MAPK pathways and induced autonomous cell growth in a cytokine-dependent cell line. E-J did not affect the transcriptional activity of EBF1 but inhibited that of PAX5. Both the physical interaction of E-J with PAX5 and kinase activity of E-J were required for E-J to inhibit PAX5 function, although the detailed mechanism of inhibition remains unclear. Importantly, gene set enrichment analysis using the results of our previous RNA-seq data of 323 primary BCR-ABL1-negative ALL samples demonstrated repression of the transcriptional target genes of PAX5 in E-J-positive ALL cells, which suggests that E-J also inhibited PAX5 function in ALL cells. Our results shed new light on the mechanisms of differentiation block by kinase fusion proteins.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción STAT / Quinasas Janus Límite: Humans Idioma: En Revista: Int J Hematol Asunto de la revista: HEMATOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción STAT / Quinasas Janus Límite: Humans Idioma: En Revista: Int J Hematol Asunto de la revista: HEMATOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón