PAWR

PRKC, apoptosis, WT1, regulator, also known as PAWR or Prostate apoptosis response-4 (Par-4), is a human gene coding for a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal cells.

PAWR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JK9
Identifiers
Aliases	PAWR, Pawr, 2310001G03Rik, PAR4, Par-4, pro-apoptotic WT1 regulator
External IDs	OMIM: 601936 MGI: 2149961 HomoloGene: 1940 GeneCards: PAWR
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q21.2 Start 79,574,979 bp[1] End 79,690,964 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 D1 Start 108,332,121 bp[2] End 108,414,240 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001106 transcription corepressor activity • leucine zipper domain binding • GO:0001948 protein binding • enzyme binding • actin binding Cellular component • cytoplasm • cell nucleus • nuclear chromatin • actin filament Biological process • regulation of transcription, DNA-templated • transcription, DNA-templated • actin filament bundle assembly • negative regulation of T cell receptor signaling pathway • negative regulation of T cell proliferation • positive regulation of amyloid precursor protein biosynthetic process • apoptotic signaling pathway • interleukin-2 biosynthetic process • negative regulation of B cell proliferation • apoptotic process • negative regulation of gene expression • negative regulation of transcription from RNA polymerase II promoter • positive regulation of cellular senescence • positive regulation of gene expression • negative regulation of fibroblast proliferation • positive regulation of hydrogen peroxide-mediated programmed cell death • positive regulation of apoptotic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5074	114774
Ensembl	ENSG00000177425	ENSMUSG00000035873
UniProt	Q96IZ0	Q925B0
RefSeq (mRNA)	NM_002583 NM_001354732 NM_001354733	NM_054056
RefSeq (protein)	NP_002574 NP_001341661 NP_001341662	NP_473397
Location (UCSC)	Chr 12: 79.57 – 79.69 Mb	Chr 10: 108.33 – 108.41 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The tumor suppressor WT1 represses and activates transcription. The protein encoded by this gene is a WT1-interacting protein that itself functions as a transcriptional repressor. It contains a putative leucine zipper domain which interacts with the zinc finger DNA binding domain of WT1. This protein is specifically upregulated during apoptosis of prostate cells.[5] The active domain of the Par-4 protein has been found to confer cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance.[6]

Interactions

PAWR has been shown to interact with:

• Apoptosis antagonizing transcription factor,[7]
• DAPK3,[8]
• Protein kinase Mζ,[9]
• SLC5A1,[10]
• THAP1,[11] and
• WT1.[12]

References

1. GRCh38: Ensembl release 89: ENSG00000177425 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035873 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: PAWR PRKC, apoptosis, WT1, regulator".
6. Zhao Y, Burikhanov R, Qiu S, Lele SM, Jennings CD, Bondada S, Spear B, Rangnekar VM (Oct 2007). "Cancer resistance in transgenic mice expressing the SAC module of Par-4". Cancer Research. 67 (19): 9276–85. doi:10.1158/0008-5472.CAN-07-2124. PMID 17909035.
7. Guo Q, Xie J (Feb 2004). "AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4". The Journal of Biological Chemistry. 279 (6): 4596–603. doi:10.1074/jbc.M309811200. PMID 14627703.
8. Kawai T, Akira S, Reed JC (Sep 2003). "ZIP kinase triggers apoptosis from nuclear PML oncogenic domains". Molecular and Cellular Biology. 23 (17): 6174–86. doi:10.1128/mcb.23.17.6174-6186.2003. PMC 180930. PMID 12917339.
9. Díaz-Meco MT, Municio MM, Frutos S, Sanchez P, Lozano J, Sanz L, Moscat J (Sep 1996). "The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C". Cell. 86 (5): 777–86. doi:10.1016/s0092-8674(00)80152-x. PMID 8797824.
10. Xie J, Guo Q (Jul 2004). "Par-4 inhibits choline uptake by interacting with CHT1 and reducing its incorporation on the plasma membrane". The Journal of Biological Chemistry. 279 (27): 28266–75. doi:10.1074/jbc.M401495200. PMID 15090548.
11. Roussigne M, Cayrol C, Clouaire T, Amalric F, Girard JP (Apr 2003). "THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies". Oncogene. 22 (16): 2432–42. doi:10.1038/sj.onc.1206271. PMID 12717420.
12. Johnstone RW, See RH, Sells SF, Wang J, Muthukkumar S, Englert C, Haber DA, Licht JD, Sugrue SP, Roberts T, Rangnekar VM, Shi Y (Dec 1996). "A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1". Molecular and Cellular Biology. 16 (12): 6945–56. doi:10.1128/mcb.16.12.6945. PMC 231698. PMID 8943350.

Further reading

• El-Guendy N, Rangnekar VM (Feb 2003). "Apoptosis by Par-4 in cancer and neurodegenerative diseases". Experimental Cell Research. 283 (1): 51–66. doi:10.1016/S0014-4827(02)00016-2. PMID 12565819.
• Bieberich E, MacKinnon S, Silva J, Noggle S, Condie BG (Aug 2003). "Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide". The Journal of Cell Biology. 162 (3): 469–79. doi:10.1083/jcb.200212067. PMC 2172704. PMID 12885759.
• Gurumurthy S, Rangnekar VM (Feb 2004). "Par-4 inducible apoptosis in prostate cancer cells". Journal of Cellular Biochemistry. 91 (3): 504–12. doi:10.1002/jcb.20000. PMID 14755681.
• Ranganathan P, Rangnekar VM (Nov 2005). "Regulation of cancer cell survival by Par-4". Annals of the New York Academy of Sciences. 1059: 76–85. doi:10.1196/annals.1339.046. PMID 16382046.
• Díaz-Meco MT, Municio MM, Frutos S, Sanchez P, Lozano J, Sanz L, Moscat J (Sep 1996). "The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C". Cell. 86 (5): 777–86. doi:10.1016/S0092-8674(00)80152-X. PMID 8797824.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Johnstone RW, See RH, Sells SF, Wang J, Muthukkumar S, Englert C, Haber DA, Licht JD, Sugrue SP, Roberts T, Rangnekar VM, Shi Y (Dec 1996). "A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1". Molecular and Cellular Biology. 16 (12): 6945–56. doi:10.1128/mcb.16.12.6945. PMC 231698. PMID 8943350.
• Guo Q, Fu W, Xie J, Luo H, Sells SF, Geddes JW, Bondada V, Rangnekar VM, Mattson MP (Aug 1998). "Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease". Nature Medicine. 4 (8): 957–62. doi:10.1038/nm0898-957. PMID 9701251.
• Johnstone RW, Tommerup N, Hansen C, Vissing H, Shi Y (Oct 1998). "Mapping of the human PAWR (par-4) gene to chromosome 12q21". Genomics. 53 (2): 241–3. doi:10.1006/geno.1998.5494. PMID 9790775.
• Kruman II, Nath A, Maragos WF, Chan SL, Jones M, Rangnekar VM, Jakel RJ, Mattson MP (Jul 1999). "Evidence that Par-4 participates in the pathogenesis of HIV encephalitis". The American Journal of Pathology. 155 (1): 39–46. doi:10.1016/s0002-9440(10)65096-1. PMC 1866661. PMID 10393834.
• Guo Q, Xie J, Chang X, Du H (May 2001). "Prostate apoptosis response-4 enhances secretion of amyloid beta peptide 1-42 in human neuroblastoma IMR-32 cells by a caspase-dependent pathway". The Journal of Biological Chemistry. 276 (19): 16040–4. doi:10.1074/jbc.M010996200. PMID 11278808.
• Chakraborty M, Qiu SG, Vasudevan KM, Rangnekar VM (Oct 2001). "Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer cell apoptosis and tumor regression". Cancer Research. 61 (19): 7255–63. PMID 11585763.
• Chang S, Kim JH, Shin J (Jan 2002). "p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition". FEBS Letters. 510 (1–2): 57–61. doi:10.1016/S0014-5793(01)03224-0. PMID 11755531.
• Ohki R, Yamamoto K, Mano H, Lee RT, Ikeda U, Shimada K (Apr 2002). "Identification of mechanically induced genes in human monocytic cells by DNA microarrays". Journal of Hypertension. 20 (4): 685–91. doi:10.1097/00004872-200204000-00026. PMID 11910304.
• Hsu SC, Kirschenbaum F, Miller J, Cordell B, McCarthy JV (Jul 2002). "Structural and functional characterization of the upstream regulatory region of the human gene encoding prostate apoptosis response factor-4". Gene. 295 (1): 109–16. doi:10.1016/S0378-1119(02)00826-0. PMID 12242017.
• Cheema SK, Mishra SK, Rangnekar VM, Tari AM, Kumar R, Lopez-Berestein G (May 2003). "Par-4 transcriptionally regulates Bcl-2 through a WT1-binding site on the bcl-2 promoter". The Journal of Biological Chemistry. 278 (22): 19995–20005. doi:10.1074/jbc.M205865200. PMID 12644474.
• Boehrer S, Chow KU, Ruthardt M, Hoelzer D, Mitrou PS, Weidmann E (Sep 2002). "Expression and function of prostate-apoptosis-response-gene-4 in lymphatic cells". Leukemia & Lymphoma. 43 (9): 1737–41. doi:10.1080/1042819021000006510. PMID 12685825.
• Roussigne M, Cayrol C, Clouaire T, Amalric F, Girard JP (Apr 2003). "THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies". Oncogene. 22 (16): 2432–42. doi:10.1038/sj.onc.1206271. PMID 12717420.
• El-Guendy N, Zhao Y, Gurumurthy S, Burikhanov R, Rangnekar VM (Aug 2003). "Identification of a unique core domain of par-4 sufficient for selective apoptosis induction in cancer cells". Molecular and Cellular Biology. 23 (16): 5516–25. doi:10.1128/MCB.23.16.5516-5525.2003. PMC 166354. PMID 12897127.