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Research Interests

연구관심분야11. Cells are highly responsive to signals from their environment.
These signals include growth factors, neuronal firing, or even the presence of bacteria or pathogens that have invaded the body.

The sensing and processing of these signals are carried out by molecular circuits within the cell that detect, amplify, and integrate the signals into a specific response.

One of the most widely used cellular responses to environmental signals is to change the phosphorylation state of specific proteins.
The level of phosphorylation of a protein is governed by two families of enzymes: protein kinases and protein phosphatases.

연구관심분야2 2. Coordinately regulated phosphorylation and dephosphorylation of the C-terminal Doamin (CTD) of RNA polymerase II is not only essential for the recruitment and assembly of transcription complexes but also temporally controls transcription and mRNAprocessing during the cell cycle. Cell-cycle effects are largely mediated through the participation of prolinedirected kinases such as cyclin-dependent kinases.

Conversely, few CTD-specific phosphatases have been identified. Fcp1 is a conserved phosphatase found in all eukaryotes and is essential for cell survival in budding and fission yeasts. Specifically, the phosphatase activity of Fcp1 is essential for recycling Pol II.

Recently, a CTD-specific phosphatase belonging to the family of Fcp1-like enzymes known as Scp1 was characterized and shown to act as an evolutionarily conserved transcriptional corepressor for inhibiting neuronal gene transcription in nonneuronal cells.

Scp1 as well as closely related family members Scp2 and Scp3 is present in neuronal progenitor cells and nonneuronal cells and targets neuronal genes by interacting with the REST/NRSF complex.

Notably, blocking Scp1 function in P19 stem cells with a dominant-negative form of Scp1 (D96ED98N) capable of binding phospho-CTD, but not catalyzing dephosphorylation, derepressed neuronal gene expression and induced neuronal differentiation of P19 stem cells.

Given Scp1’'s role in limiting inappropriate expression of neuronalspecific genes in pluripotent cells and its marked downregulation as these cells initiate neuronal differentiation, Scp1 serves as a target for small molecule inhibitors.

Phosphatidylinositol (PI) lipids serve structural roles in biological membranes as well as playing important roles as signaling molecules.
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates cell motility, cell shape, vesicle turnover, and membrane excitability either through directly binding to target proteins or by mediating calcium signaling via its cleavage by phospholipase C into inositol 1,4,5-trisphosphate and diacylglycerol. Phosphatidylinositol 3,4,5-trisphosphate[PI(3,4,5)P3] regulates cell proliferation, survival, and morphology.

To exert physiological roles, the concentrations of these phosphoinositides in membranes are strictly regulated by multiple kinases and phosphatases. Recently, we identified a phosphoinositide phosphatase, Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP), consisting of an ion channel-like transmembrane domain followed by a phosphatase domain which shares sequence identity to the phosphatase and tensin homolog deleted on chromosome 10q23 (PTEN).

PTEN is a well characterized PI phosphatase that dephosphorylates the phosphate on the 3 position of PI(3,4,5)P3, resulting in generation of PI(4,5)P2. Ci-VSP shares overlapping substrate specificity with PTEN in that it was also shown to dephosphorylate PI(3,4,5)P3.

Research Methodology
  • Biochemical Method
  • Kinetics
  • Structural Identification
  • Cell Biology
  • Bioinformatics
  • Mass Spectrometry
  • Lipidomics
  • Systems Biology