ZFIN ID: ZDB-PUB-140524-5
Characterization of the human oncogene SCL/TAL1 interrupting locus (Stil) mediated Sonic hedgehog (Shh) signaling transduction in proliferating mammalian dopaminergic neurons
Sun, L., Carr, A.L., Li, P., Lee, J., McGregor, M., Li, L.
Date: 2014
Source: Biochemical and Biophysical Research Communications   449(4): 444-8 (Journal)
Registered Authors: Li, Lei
Keywords: Cell proliferation, Dopaminergic neurons, PC12, Stil gene expression
MeSH Terms:
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Dopaminergic Neurons/cytology
  • Dopaminergic Neurons/physiology*
  • Hedgehog Proteins/physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • PC12 Cells
  • Rats
  • Repressor Proteins/metabolism
  • Signal Transduction*
  • Transcription Factors/metabolism
PubMed: 24853807 Full text @ Biochem. Biophys. Res. Commun.
ABSTRACT
The human oncogene SCL/TAL1 interrupting locus (Stil) is highly conserved in all vertebrate species. In humans, the expression of Stil is involved in cancer cell survival, apoptosis and proliferation. In this research, we investigated the roles of Stil expression in cell proliferation of mammalian dopaminergic (DA) PC12 cells. Stil functions through the Sonic hedgehog (Shh) signal transduction pathway. Co-immunoprecipitation tests revealed that STIL interacts with Shh downstream components, which include SUFU and GLI1. By examining the expression of Stil, Gli1, CyclinD2 (cell-cycle marker) and PCNA (proliferating cell nuclear antigen), we found that up-regulation of Stil expression (transfection with overexpression plasmids) increased Shh signaling transduction and PC12 cell proliferation, whereas down-regulation of Stil expression (by shRNA) inhibited Shh signaling transduction, and thereby decreased PC12 cell proliferation. Transient transfection of PC12 cells with Stil knockdown or overexpression plasmids did not affect PC12 cell neural differentiation, further indicating the specific roles of Stil in cell proliferation. The results from this research suggest that Stil may serve as a bio-marker for neurological diseases involved in DA neurons, such as Parkinson's disease.
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