Related Experiment Videos
Pim-1 translocates sorting nexin 6/TRAF4-associated factor 2 from cytoplasm to nucleus
1Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Abstract:
Pim-1, an oncogene product of serine/threonine kinase, has been found to play roles in apoptosis induction/suppression, cell-cycle progression and transcriptional regulation by phosphorylating the target proteins involved in these processes. The target proteins phosphorylated by Pim-1, including p100, Cdc25A, PAP-1 and heterochromatin protein 1, have been identified. The precise functions of Pim-1, however, are still poorly understood. In this study, we identified tumor necrosis factor receptor-associated factor 4-associated factor 2/sorting nexin 6 (TFAF2/SNX6) as a Pim-1-binding protein, and we found that TFAF2/SNX6 was phosphorylated and translocated from the cytoplasm to nucleus by Pim-1. This translocation of the protein was not affected by Pim-1-dependent phosphorylation. Since sorting nexins, including TFAF2/SNX6, have been reported to be located in the cytoplasm or membrane by association with several receptors of tyrosine- or serine/threonine-kinase, this is the first report of TFAF2/SNX6 being located in the nucleus after binding to Pim-1.
Insights
The serine/threonine kinase Pim-1 phosphorylates tumor necrosis factor receptor-associated factor 4-associated factor 2/sorting nexin 6 (TFAF2/SNX6). Pim-1 induces TFAF2/SNX6 translocation from the cytoplasm to the nucleus.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Pim-1 is a serine/threonine kinase involved in apoptosis, cell cycle, and transcription.
- Pim-1 phosphorylates various target proteins, but its precise functions remain unclear.
- Sorting nexins, including TFAF2/SNX6, are typically cytoplasmic or membrane-associated.
Purpose of the Study:
- To identify novel Pim-1 binding proteins.
- To investigate the interaction between Pim-1 and TFAF2/SNX6.
- To elucidate the subcellular localization changes of TFAF2/SNX6 upon binding to Pim-1.
Main Methods:
- Co-immunoprecipitation to identify Pim-1 binding partners.
- Western blotting to detect protein phosphorylation.
- Immunofluorescence microscopy to track protein translocation.
Main Results:
- TFAF2/SNX6 was identified as a novel Pim-1 binding protein.
- Pim-1 phosphorylates TFAF2/SNX6.
- Pim-1 induces the translocation of TFAF2/SNX6 from the cytoplasm to the nucleus.
- This translocation is independent of Pim-1-mediated phosphorylation.
Conclusions:
- Pim-1 interacts with and phosphorylates TFAF2/SNX6.
- Pim-1 induces nuclear translocation of TFAF2/SNX6, a novel localization for this protein.
- This finding expands the known functions of Pim-1 and the subcellular localization of sorting nexins.