PAWR
Description
The PAWR (pro-apoptotic WT1 regulator) is a protein-coding gene located on chromosome 12.
PAWR, or Prostate apoptosis response-4, is a tumor-suppressor protein encoded by the PAWR gene in humans. It induces apoptosis in cancer cells but not in normal cells. PAWR interacts with the tumor suppressor WT1, which both represses and activates transcription. PAWR functions as a transcriptional repressor and contains a leucine zipper domain that interacts with the zinc finger DNA binding domain of WT1. It is specifically upregulated during apoptosis of prostate cells. The active domain of PAWR has been shown to confer cancer resistance in transgenic mice without compromising normal viability or aging, suggesting its therapeutic potential.
PAWR is a pro-apoptotic protein that selectively induces apoptosis in cancer cells, sensitizing them to various apoptotic stimuli and causing tumor regression in animal models. It activates the Fas prodeath pathway and concurrently inhibits NF-kappa-B transcriptional activity in certain cancer cells, leading to apoptosis. PAWR also inhibits transcriptional activation and enhances transcriptional repression mediated by WT1, downregulating the anti-apoptotic protein BCL2 through its interaction with WT1. Additionally, it functions as a transcriptional repressor itself and may directly regulate the amyloid precursor protein (APP) cleavage activity of BACE1.
PAWR is also known as PAR4, Par-4.
