Structural highlights
Function
PAWR_RAT Pro-apoptopic 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 (By similarity).
Publication Abstract from PubMed
Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4CC), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4CC contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4NES) sequence, which is masked upon dimerization indicating a potential mechanism for nuclear localization. The heteromeric-interaction models specifically showed that charge interaction is an important factor in the stability of heteromers of the C-terminal leucine zipper subdomain of Par-4 (Par-4LZ). These heteromer models also displayed NES masking capacity and therefore the ability to influence intracellular localization.
Structural basis for the regulatory interactions of proapoptotic Par-4.,Tiruttani Subhramanyam UK, Kubicek J, Eidhoff UB, Labahn J Cell Death Differ. 2017 Sep;24(9):1540-1547. doi: 10.1038/cdd.2017.76. Epub 2017 , Jun 16. PMID:28622290[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tiruttani Subhramanyam UK, Kubicek J, Eidhoff UB, Labahn J. Structural basis for the regulatory interactions of proapoptotic Par-4. Cell Death Differ. 2017 Sep;24(9):1540-1547. doi: 10.1038/cdd.2017.76. Epub 2017 , Jun 16. PMID:28622290 doi:http://dx.doi.org/10.1038/cdd.2017.76
