PAWR

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)
End	79,690,964 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	108,250,101 bp
RNA expression pattern
	Top expressed in
	germinal epithelium; ; saphenous vein; ; right coronary artery; ; sural nerve; ; left uterine tube; ; myometrium; ; parietal pleura; ; left coronary artery; ; corpus epididymis; ; canal of the cervix;
	Top expressed in
	cumulus cell; ; Paneth cell; ; hair follicle; ; medullary collecting duct; ; renal corpuscle; ; ascending aorta; ; calvaria; ; lacrimal gland; ; left colon; ; conjunctival fornix;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	transcription corepressor activity; leucine zipper domain binding; protein binding; enzyme binding; actin binding;
Cellular component	cytoplasm; nucleus; 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; negative regulation of B cell proliferation; apoptotic process; negative regulation of gene expression; negative regulation of transcription by RNA polymerase II; 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
	5074
	114774
	ENSG00000177425
	ENSMUSG00000035873
	Q96IZ0
	Q925B0
	NM_002583; NM_001354732; NM_001354733
	NM_054056
	NP_002574; NP_001341661; NP_001341662
	NP_473397
	Wikidata
View/Edit Human	View/Edit Mouse

PRKC apoptosis WT1 regulator protein, or Prostate apoptosis response-4, is a tumor-suppressor protein coded for in the human by the PAWR gene, that induces apoptosis in cancer cells, but not in normal cells.

Function[edit]

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[edit]

PAWR has been shown to interact with:

References[edit]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000177425 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000035873 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: PAWR PRKC, apoptosis, WT1, regulator".
^ 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.
^ 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.
^ 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.
^ 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. S2CID 15675524.
^ 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.
^ 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. S2CID 25237333.
^ 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[edit]

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. S2CID 31578703.
Ranganathan P, Rangnekar VM (Nov 2005). "Regulation of cancer cell survival by Par-4". Annals of the New York Academy of Sciences. 1059 (1): 76–85. Bibcode:2005NYASA1059...76R. doi:10.1196/annals.1339.046. PMID 16382046. S2CID 26538481.
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. S2CID 15675524.
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. S2CID 1621858.
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. S2CID 85579338.
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. S2CID 34968458.
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. S2CID 45232765.
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. S2CID 25237333.
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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000177425 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[entrez-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.

[pmid14627703-7] 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.

[pmid12917339-8] 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.

[pmid8797824-9] 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. S2CID 15675524.

[pmid15090548-10] 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.

[pmid12717420-11] 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. S2CID 25237333.

[pmid8943350-12] 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.

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