Pro-apoptotic WT1 regulator (PAWR)

The **Pro-apoptotic WT1 regulator (PAWR, also known as Par-4)** is a tumor suppressor protein that selectively induces apoptosis in cancer cells through both intracellular and extracellular mechanisms. Intracellularly, PAWR inhibits pro-survival pathways (notably NF-κB) and activates the Fas-mediated apoptosis pathway. It also acts as a transcriptional corepressor through interaction with WT1 and can downregulate anti-apoptotic BCL2, contributing to cancer cell death. Extracellularly, a secreted form of PAWR binds to the cell surface receptor GRP78, inducing apoptosis in neighboring cells via the extrinsic pathway. PAWR's activation, localization, and post-translational modifications are crucial for its selective apoptotic activity in tumors and neuronally differentiated cells. The gene is frequently silenced or mutated in cancer and is implicated in therapeutic resistance, highlighting its role as a promising drug target for cancer-selective pro-apoptotic therapies[1][2][3][4].

Other names

PAR4Par-4PRKC apoptosis WT1 regulator proteinProstate apoptosis response 4 proteinWT1-interacting proteinTranscriptional repressor PAR4Prostate apoptosis response protein 4PAWR_HUMAN

Activation of Fas pro-death pathway; Inhibition of pro-survival pathways (NF-κB signaling); Extracellular binding of PAWR to GRP78, triggering extrinsic apoptosis; Sensitization of cancer cells to apoptotic stimuli