Characterization of the human oncogene SCL/TAL1 interrupting locus (Stil) mediated Sonic hedgehog (Shh) signaling transduction in proliferating mammalian dopaminergic neurons.
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.
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Physiology, Nankai University School of Medicine, Tianjin 300071, China.
Lei
L
Sun
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA; Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USA.
Aprell L
AL
Carr
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
Ping
P
Li
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
Jessica
J
Lee
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
Mary
M
McGregor
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA; Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: Li.78@nd.edu.
Lei
L
Li
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D059290:Dopaminergic Neurons / Q000166:cytology / Q000502:physiology*; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C071236:STIL protein, human; C490764:SUFU protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1
Cell proliferation; Dopaminergic neurons; PC12; Stil gene expression