PAWR

From Wikipedia, the free encyclopedia

PRKC, apoptosis, WT1, regulator

Identifiers

PAWR; PAR4; Par-4

External IDs

OMIM: 601936 MGI: 2149961 HomoloGene: 1940

Gene ontology
Molecular Function:	• transcription corepressor activity • enzyme binding
Cellular Component:	• nucleus • cytoplasm
Biological Process:	• negative regulation of transcription from RNA polymerase II promoter • transcription • regulation of transcription, DNA-dependent • apoptosis • negative regulation of cell proliferation • negative regulation of B cell proliferation • interleukin-2 biosynthetic process • negative regulation of T cell proliferation • positive regulation of amyloid precursor protein biosynthetic process • positive regulation of apoptosis • negative regulation of T cell receptor signaling pathway

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_002583 (mRNA)
NP_002574 (protein)

NM_054056 (mRNA)
NP_473397 (protein)

Location

Chr 12: 78.51 - 78.61 Mb

Chr 10: 107.74 - 107.82 Mb

Pubmed search

[1]

[2]

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.

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.^[1] 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.^[2]

[edit] References

^ Entrez Gene: PAWR PRKC, apoptosis, WT1, regulator.
^ Zhao Y, Burikhanov R, Qiu S, Lele SM, Jennings CD, Bondada S, Spear B, Rangnekar VM. 2007. Cancer resistance in transgenic mice expressing the SAC module of Par-4. Cancer Res. 67(19):9276-85

[edit] Further reading

El-Guendy N, Rangnekar VM (2003). "Apoptosis by Par-4 in cancer and neurodegenerative diseases.". Exp. Cell Res. 283 (1): 51–66. PMID 12565819.
Gurumurthy S, Rangnekar VM (2004). "Par-4 inducible apoptosis in prostate cancer cells.". J. Cell. Biochem. 91 (3): 504–12. doi:10.1002/jcb.20000. PMID 14755681.
Ranganathan P, Rangnekar VM (2006). "Regulation of cancer cell survival by Par-4.". Ann. N. Y. Acad. Sci. 1059: 76–85. doi:10.1196/annals.1339.046. PMID 16382046.
Díaz-Meco MT, Municio MM, Frutos S, et al. (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. PMID 8797824.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. PMID 8889548.
Johnstone RW, See RH, Sells SF, et al. (1997). "A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1.". Mol. Cell. Biol. 16 (12): 6945–56. PMID 8943350.
Guo Q, Fu W, Xie J, et al. (1998). "Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease.". Nat. Med. 4 (8): 957–62. PMID 9701251.
Johnstone RW, Tommerup N, Hansen C, et al. (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, et al. (1999). "Evidence that Par-4 participates in the pathogenesis of HIV encephalitis.". Am. J. Pathol. 155 (1): 39–46. PMID 10393834.
Guo Q, Xie J, Chang X, Du H (2001). "Prostate apoptosis response-4 enhances secretion of amyloid beta peptide 1-42 in human neuroblastoma IMR-32 cells by a caspase-dependent pathway.". J. Biol. Chem. 276 (19): 16040–4. doi:10.1074/jbc.M010996200. PMID 11278808.
Chakraborty M, Qiu SG, Vasudevan KM, Rangnekar VM (2001). "Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer cell apoptosis and tumor regression.". Cancer Res. 61 (19): 7255–63. PMID 11585763.
Chang S, Kim JH, Shin J (2002). "p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition.". FEBS Lett. 510 (1-2): 57–61. PMID 11755531.
Ohki R, Yamamoto K, Mano H, et al. (2002). "Identification of mechanically induced genes in human monocytic cells by DNA microarrays.". J. Hypertens. 20 (4): 685–91. PMID 11910304.
Hsu SC, Kirschenbaum F, Miller J, et al. (2003). "Structural and functional characterization of the upstream regulatory region of the human gene encoding prostate apoptosis response factor-4.". Gene 295 (1): 109–16. PMID 12242017.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
Cheema SK, Mishra SK, Rangnekar VM, et al. (2003). "Par-4 transcriptionally regulates Bcl-2 through a WT1-binding site on the bcl-2 promoter.". J. Biol. Chem. 278 (22): 19995–20005. doi:10.1074/jbc.M205865200. PMID 12644474.
Boehrer S, Chow KU, Ruthardt M, et al. (2003). "Expression and function of prostate-apoptosis-response-gene-4 in lymphatic cells.". Leuk. Lymphoma 43 (9): 1737–41. PMID 12685825.
Roussigne M, Cayrol C, Clouaire T, et al. (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, et al. (2003). "Identification of a unique core domain of par-4 sufficient for selective apoptosis induction in cancer cells.". Mol. Cell. Biol. 23 (16): 5516–25. PMID 12897127.