PAWR
Domain
The leucine-zipper domain is not essential for apoptosis, but is required for sensitization of cells to exogenous apoptotic insults and for interaction with its partners.
The SAC domain is a death-inducing domain selective for apoptosis induction in cancer cells. This domain is essential for nuclear entry, Fas activation, inhibition of NF-kappa-B activity and induction of apoptosis in cancer cells (By similarity).
The B30.2/SPRY domain-binding motif mediates recognition by proteins containing a B30.2/SPRY domain.
Function
Pro-apoptotic protein capable of selectively inducing apoptosis in cancer cells, sensitizing the cells to diverse apoptotic stimuli and causing regression of tumors in animal models. Induces apoptosis in certain cancer cells by activation of the Fas prodeath pathway and coparallel inhibition of NF-kappa-B transcriptional activity. Inhibits the transcriptional activation and augments the transcriptional repression mediated by WT1. Down-regulates the anti-apoptotic protein BCL2 via its interaction with WT1. Seems also to be a transcriptional repressor by itself. May be directly involved in regulating the amyloid precursor protein (APP) cleavage activity of BACE1.
Post-translational modifications
Preferentially phosphorylated at the Thr-163 by PKC in cancer cells.
Tissue Specificity
Widely expressed. Expression is elevated in various neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer, Parkinson and Huntington diseases and stroke. Down-regulated in several cancers.
Cellular localization
- Cytoplasm
- Nucleus
- Mainly cytoplasmic in absence of apoptosis signal and in normal cells. Nuclear in most cancer cell lines. Nuclear entry seems to be essential but not sufficient for apoptosis (By similarity). Nuclear localization includes nucleoplasm and PML nuclear bodies.
Alternative names
PAR4, PAWR, PRKC apoptosis WT1 regulator protein, Prostate apoptosis response 4 protein, Par-4