Your browser doesn't support javascript.
loading
NUP98-BPTF promotes oncogenic transformation through PIM1 upregulation.
Noura, Mina; Tomita, Sakura; Yasuda, Takahiko; Tsuzuki, Shinobu; Kiyoi, Hitoshi; Hayakawa, Fumihiko.
Afiliación
  • Noura M; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Tomita S; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Yasuda T; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
  • Tsuzuki S; Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan.
  • Kiyoi H; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Hayakawa F; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Med ; 13(13): e7445, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38940430
ABSTRACT

INTRODUCTION:

Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and contribute to leukemogenesis via aberrant transcriptional regulation. We previously identified NUP98-BPTF (NB) fusion in patients with T-cell acute lymphoblastic leukemia (T-ALL) using next-generation sequencing. The FG-repeat of NUP98 and the PHD finger and bromodomain of bromodomain PHD finger transcription factor (BPTF) are retained in the fusion. Like other NUP98 fusion proteins, NB is considered to regulate genes that are essential for leukemogenesis. However, its target genes or pathways remain unknown. MATERIALS AND

METHODS:

To investigate the potential oncogenic properties of the NB fusion protein, we lentivirally transduced a doxycycline-inducible NB expression vector into mouse NIH3T3 fibroblasts and human Jurkat T-ALL cells.

RESULTS:

NB promoted the transformation of mouse NIH3T3 fibroblasts by upregulating the proto-oncogene Pim1, which encodes a serine/threonine kinase. NB transcriptionally regulated Pim1 expression by binding to its promoter and activated MYC and mTORC1 signaling. PIM1 knockdown or pharmacological inhibition of mTORC1 signaling suppressed NB-induced NIH3T3 cell transformation. Furthermore, NB enhanced the survival of human Jurkat T-ALL cells by inactivating the pro-apoptotic protein BCL2-associated agonist of cell death (BAD).

CONCLUSION:

We demonstrated the pivotal role of NB in cell transformation and survival and identified PIM1as a key downstream target of NB. These findings propose a promising therapeutic strategy for patients with NB fusion-positive leukemia.
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: Proteínas de Fusión Oncogénica / Transformación Celular Neoplásica / Proteínas de Complejo Poro Nuclear / Proteínas Proto-Oncogénicas c-pim-1 Límite: Animals / Humans Idioma: En Revista: Cancer Med Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
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: Proteínas de Fusión Oncogénica / Transformación Celular Neoplásica / Proteínas de Complejo Poro Nuclear / Proteínas Proto-Oncogénicas c-pim-1 Límite: Animals / Humans Idioma: En Revista: Cancer Med Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos