PARIS/ZNF746 (F7U7T) Rabbit Monoclonal Antibody #17821

Parkin-interacting substrate (PARIS), also known as Zinc finger protein 746 (ZNF746), is a tightly regulated transcriptional repressor. Structurally, PARIS/ZNF746 contains an N-terminal Krüppel-associated box (KRAB) domain and four zinc finger domains. The zinc finger domains promote DNA binding, while the KRAB domain mediates its repressor activity. PARIS/ZNF746 binds insulin response sequences (IRS) within the promoter region of peroxisome-proliferator activated receptor gamma coactivator-1 alpha (PGC-1 alpha), downregulating its expression (1,2). PGC-1 alpha is a master regulator of mitochondrial biogenesis, which is important for combating the buildup of reactive oxygen species (ROS) and maintaining cellular homeostasis. Aggregation of toxic protein species, including alpha-synuclein in Parkinson’s disease (PD), leads to ROS buildup. PGC-1 alpha overexpression has been shown to be protective in PD models. PARIS/ZNF746 regulation of PGC-1 alpha expression is mediated by PTEN induced putative kinase 1 (PINK1) and Parkin. PINK1 phosphorylates PARIS/ZNF746, leading to ubiquitination by Parkin and degradation by the proteasome. Dysfunction or deletion of PINK1 or Parkin leads to PARIS accumulation, PGC-1 alpha repression, and the degeneration of dopaminergic neurons in PD models (3-5).