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Updated: Oct 2, 2026

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase
Eeva-Marja Rainio1, Jouko Sandholm, Päivi J Koskinen
1Turku Centre for Biotechnology, University of Turku/Abo Akademi University, and Turku Graduate School of Biomedical Sciences, Turku, Finland.
Abstract:
Pim-1 is an oncogenic serine/threonine kinase implicated in cytokine-induced signal transduction and in development of lymphoid malignancies. However, its precise function as well as physiological substrates have remained unknown. In this study we demonstrate that Pim-1 can physically interact with the NFATc1 transcription factor and phosphorylate it in vitro on several serine residues. In contrast to previously recognized NFATc kinases, wild-type Pim-1 enhances NFATc-dependent transactivation and IL-2 production in Jurkat T cells, while kinase-deficient Pim-1 mutants inhibit them in a dominant negative fashion. Our results reveal a novel, phosphorylation-dependent regulatory mechanism targeting NFATc1 through which Pim-1 acts as a downstream effector of Ras to facilitate IL-2-dependent proliferation and/or survival of lymphoid cells.
Insights
The oncogenic kinase Pim-1 interacts with and phosphorylates the NFATc1 transcription factor. This phosphorylation enhances interleukin-2 (IL-2) production and lymphoid cell proliferation, revealing a novel regulatory pathway.
Area of Science:
- Molecular Biology
- Immunology
- Oncology
Background:
- Pim-1 is an oncogenic serine/threonine kinase involved in signal transduction and lymphoid malignancies.
- The exact function and physiological substrates of Pim-1 remain largely unknown.
Purpose of the Study:
- To investigate the interaction between Pim-1 and the NFATc1 transcription factor.
- To elucidate the role of Pim-1 in regulating NFATc1 activity and its downstream effects on lymphoid cells.
Main Methods:
- Co-immunoprecipitation to assess physical interaction between Pim-1 and NFATc1.
- In vitro kinase assays to determine phosphorylation of NFATc1 by Pim-1.
- Reporter gene assays in Jurkat T cells to measure NFATc1-dependent transactivation and IL-2 production.
Main Results:
- Pim-1 physically interacts with NFATc1.
- Pim-1 phosphorylates NFATc1 on multiple serine residues in vitro.
- Wild-type Pim-1 enhances NFATc1-dependent transactivation and IL-2 production, while kinase-deficient mutants inhibit these processes.
Conclusions:
- Pim-1 regulates NFATc1 activity through phosphorylation, representing a novel regulatory mechanism.
- Pim-1 acts as a downstream effector of Ras, facilitating IL-2-dependent proliferation and survival in lymphoid cells.
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