PAWR

PAWR is a tumor suppressor protein that selectively induces apoptosis in cancer cells through intracellular and extracellular mechanisms. The intracellular mechanism involves the inhibition of pro-survival pathways and the activation of Fas-mediated apoptosis, while the extracellular mechanism involves the binding of a secreted form of this protein to glucose regulated protein 78 (GRP78) on the cell surface, which leads to activation of the extrinsic apoptotic pathway. This gene is located on the unstable human chromosomal 12q21 region and is often deleted or mutated different tumors. The encoded protein also plays an important role in the progression of age-related diseases.

PAWR

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.

Actin filament bundle assemblyISS:UniProtKB
Apoptotic processISS:UniProtKB
Apoptotic signaling pathwayIEA:Ensembl
Negative regulation of B cell proliferationIEA:Ensembl
Negative regulation of fibroblast proliferationIEA:Ensembl
Negative regulation of gene expressionIEA:Ensembl
Negative regulation of T cell proliferationIEA:Ensembl
Negative regulation of T cell receptor signaling pathwayIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentTAS:ProtInc
Positive regulation of amyloid precursor protein biosynthetic processIEA:Ensembl
Positive regulation of apoptotic processManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of cellular senescenceIEA:Ensembl
Positive regulation of gene expressionIEA:Ensembl
Positive regulation of hydrogen peroxide-mediated programmed cell deathIEA:Ensembl

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.

Preferentially phosphorylated at the Thr-163 by PKC in cancer cells.