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Lymphocyte quiescence factor Dpp2 is transcriptionally activated by KLF2 and TOB1
Pradeep Bista1, Deanna A Mele, Diana Velez Baez
1Graduate Program in Immunology, Department of Pathology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, United States.
Dipeptidyl peptidase 2 (DPP2) transcription is regulated by cell contact and serum levels, essential for quiescent lymphocyte survival. Lung Kruppel-like factor (KLF2) and TOB1 activate DPP2, linking quiescence to its enzymatic activity.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Dipeptidyl peptidase 2 (DPP2) activity is crucial for quiescent lymphocyte survival but not activated ones.
- This suggests cell cycle-specific regulation of DPP2, prompting investigation into its transcriptional control.
Purpose of the Study:
- To investigate the cell cycle-specific regulation of dipeptidyl peptidase 2 (DPP2) transcription.
- To determine the role of contact inhibition, serum starvation, KLF2, and TOB1 in regulating Dpp2 transcription.
Main Methods:
- Utilized NIH-3T3 cells for promoter-reporter assays to assess Dpp2 transcriptional activity.
- Examined endogenous Dpp2 transcript levels under conditions of contact inhibition and serum starvation.
- Investigated the impact of lung Kruppel-like factor (KLF2) and TOB1 on Dpp2 promoter activity using reporter systems.
- Analyzed DPP2 transcript levels in human peripheral blood mononuclear cells (PBMCs) following T cell receptor activation.
Main Results:
- Dpp2 transcription and promoter activity were enhanced in NIH-3T3 cells upon contact inhibition or serum starvation.
- KLF2 and TOB1 were identified as activators of the mouse Dpp2 promoter.
- Endogenous DPP2 transcript levels decreased in human PBMCs upon T cell receptor activation compared to resting cells.
Conclusions:
- Dpp2 transcription is dependent on cell contact and serum availability.
- KLF2 and TOB1 are linked to the regulation of Dpp2 transcription in quiescent cells.
- These findings connect quiescence-specific transcriptional elements to the essential role of DPP2 activity in non-dividing lymphocytes.
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