Parkinson�s disease (PD) is one of the major neurodegenerative disorders. Mitochondrial malfunction is implicated in\nPD pathogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1\n(PINK1), a serine/threonine kinase, plays an important role in the quality control of mitochondria and more than 70\nPINK1 mutations have been identified to cause early-onset PD. However, the regulation of PINK1 gene expression\nremains elusive. In the present study, we identified the transcription start site (TSS) of the human PINK1 gene using\nswitching mechanism at 5�end of RNA transcription (SMART RACE) assay. The TSS is located at 91 bp upstream of\nthe translation start site ATG. The region with 104 bp was identified as the minimal promoter region by deletion\nanalysis followed by dual luciferase assay. Four functional cis-acting nuclear factor kappa-light-chain-enhancer of\nactivated B cells (NFkB)-binding sites within the PINK1 promoter were identified. NFkB overexpression led to the\nup-regulation of PINK1 expression in both HEK293 cells and SH-SY5Y cells. Consistently, lipopolysaccharide (LPS), a\nstrong activator of NFkB, significantly increased PINK1 expression in SH-SY5Y cells. Taken together, our results clearly\nsuggested that PINK1 expression is tightly regulated at its transcription level and NFkB is a positive regulator for\nPINK1 expression.
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