[논문]암 치료 표적으로써 prostate apoptosis response-4 (Par-4)

우선민; 권택규

doi:10.5352/jls.2015.25.8.947

암 치료 표적으로써 prostate apoptosis response-4 (Par-4)
Prostate Apoptosis Response-4 (Par-4) as a Cancer Therapeutic Target 원문보기

생명과학회지 = Journal of life science, v.25 no.8 = no.184, 2015년, pp.947 - 952

우선민 (계명대학교 의과대학 면역학교실) , 권택규 (계명대학교 의과대학 면역학교실)

초록
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Par-4는 종양 억제 유전자로 암세포 선택적으로 세포사멸을 증진하는 기능을 가진다. Par-4 유전자는 nuclear localization sequences (NLS), leucine zipper (LZ), nuclear export sequence (NES), selective for apoptosis in cancer cells (SAC)의 네 가지 도메인을 가지고 있다. 이 중에서도 SAC 도메인이 Par-4에 의한 세포사멸에 중요한 역할을 하며, 이러한 Par-4의 활성화는 세포 내 경로와 세포 외 경로로 나누어진다. 세포질 내의 Par-4는 핵 내로 이동하여 NF-κB 매개의 세포 성장 경로를 억제하고 세포 밖으로 분비된 Par-4는 세포 표면에 존재하는 수용체인 GRP78과 결합하여 세포 사멸을 유도한다. 따라서 Par-4의 발현을 증가시키는 물질에 의한 세포 사멸뿐만 아니라 암세포에서 발현이 낮은 Par-4의 과발현을 통하여 세포사멸 민감화가 증진된다. 따라서 Par-4는 암 치료의 강력한 표적으로의 가능성을 가지고 있다.

Abstract ▼ AI-Helper

Prostate apoptosis response-4 (Par-4) was originally identified in androgen-independent prostate cancer cells undergoing apoptosis. Par-4 is ubiquitously expressed in normal cells and tissues, but it is downregulated in several types of cancers. Par-4 is a 38 kDa tumor suppressor protein encoded by the PARW gene. Par-4 promotes apoptosis in a variety of cancerous cells, but not in normal cells. In this review, we focused on the structure, expression and function of Par-4 in apoptotic signaling pathway. Functional domains of Par-4 include two nuclear localization sequences (NLS), a leucine zipper (LZ) domain, a nuclear export sequence (NES) and selective for apoptosis in cancer cell (SAC) domain. Many studies have underlined the importance of Par-4 in preventing cancer development. The activity of Par-4 is differently regulated by localization of intracellular and extracellular Par-4. Intracellular Par-4 inhibits Akt- and NF-κB-mediated cell survival pathways and downregulates Bcl-2 expression. Extracellular Par-4 activates the extrinsic apoptotic pathway by binding to cell surface receptor GRP78, a stress response protein that is in the endoplasmic reticulum (ER). Endogenous Par-4 sensitizes cancer cells to various apoptotic stimuli, while exogenous Par-4 enhances SAC domain-dependent apoptosis in cancer cells, but not normal cells. Therefore, Par-4 is an attractive target for cancer therapy.

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이론/모형

[3, 23, 28, 45]. 본 보고에서는 Par-4의 구조적 기능과 항암효과 및 작용 기전에 대하여 정리하였다.

참고문헌 (51)

Ahmed, M. M., Sheldon, D., Fruitwala, M. A., Venkatasubbarao, K., Lee, E. Y., Gupta, S., Wood, C., Mohiuddin, M. and Strodel, W. E. 2008. Downregulation of PAR-4, a pro-apoptotic gene, in pancreatic tumors harboring K-ras mutation. Int. J. Cancer 122, 63-70.

상세보기
Almoguera, C., Shibata, D., Forrester, K., Martin, J., Arnheim, N. and Perucho, M. 1988. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53, 549-554.

상세보기
Azmi, A. S., Ahmad, A., Banerjee, S., Rangnekar, V. M., Mohammad, R. M. and Sarkar, F. H. 2008. Chemoprevention of pancreatic cancer: characterization of Par-4 and its modulation by 3,3′ diindolylmethane (DIM). Pharm. Res. 25, 2117-2124.

상세보기
Barkett, M. and Gilmore, T. D. 1999. Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene 18, 6910-6924.

상세보기
Barradas, M., Monjas, A., Diaz-Meco, M. T., Serrano, M. and Moscat, J. 1999. The downregulation of the pro-apoptotic protein Par-4 is critical for Ras-induced survival and tumor progression. EMBO J. 18, 6362-6369.

상세보기
Boehrer, S., Chow, K. U., Puccetti, E., Ruthardt, M., Godzisard, S., Krapohl, A., Schneider, B., Hoelzer, D., Mitrou, P. S., Rangnekar, V. M. and Weidmann, E. 2001. Deregulated expression of prostate apoptosis response gene-4 in less differentiated lymphocytes and inverse expressional patterns of par-4 and bcl-2 in acute lymphocytic leukemia. Hematol. J. 2, 103-107.
Bos, J. L. 1989. ras oncogenes in human cancer: a review. Cancer Res. 49, 4682-4689.

상세보기
Burikhanov, R., Zhao, Y., Goswami, A., Qiu, S., Schwarze, S. R. and Rangnekar, V. M. 2009. The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis. Cell 138, 377-388.

상세보기
Chakraborty, M., Qiu, S. G., Vasudevan, K. M. and Rangnekar, V. M. 2001. Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer cell apoptosis and tumor regression. Cancer Res. 61, 7255-7263.

상세보기
Chaudhry, P., Singh, M., Parent, S. and Asselin, E. 2012. Prostate apoptosis response 4 (Par-4), a novel substrate of caspase-3 during apoptosis activation. Mol. Cell. Biol. 32, 826-839.

상세보기
Cheema, S. K., Mishra, S. K., Rangnekar, V. M., Tari, A. M., Kumar, R. and Lopez-Berestein, G. 2003. Par-4 transcriptionally regulates Bcl-2 through a WT1-binding site on the bcl-2 promoter. J. Biol. Chem. 278, 19995-20005.

상세보기
Cook, J., Krishnan, S., Ananth, S., Sells, S. F., Shi, Y., Walther, M. M., Linehan, W. M., Sukhatme, V. P., Weinstein, M. H. and Rangnekar, V. M. 1999. Decreased expression of the pro-apoptotic protein Par-4 in renal cell carcinoma. Oncogene 18, 1205-1208.

상세보기
de Thonel, A., Hazoume, A., Kochin, V., Isoniemi, K., Jego, G., Fourmaux, E., Hammann, A., Mjahed, H., Filhol, O., Micheau, O., Rocchi, P., Mezger, V., Eriksson, J. E., Rangnekar, V. M. and Garrido, C. 2014. Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells. Cell Death Dis. 5, e1016.

상세보기
Diaz-Meco, M. T., Lallena, M. J., Monjas, A., Frutos, S. and Moscat, J. 1999. Inactivation of the inhibitory kappaB protein kinase/nuclear factor kappaB pathway by Par-4 expression potentiates tumor necrosis factor alpha-induced apoptosis. J. Biol .Chem. 274, 19606-19612.

상세보기
Diaz-Meco, M. T. and Moscat, J. 2008. Akt regulation and lung cancer: a novel role and mechanism of action for the tumor suppressor Par-4. Cell Cycle 7, 2817-2820.

상세보기
Diaz-Meco, M. T., Municio, M. M., Frutos, S., Sanchez, P., Lozano, J., Sanz, L. and Moscat, J. 1996. The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C. Cell 86, 777-786.

상세보기
Donninger, H., Hesson, L., Vos, M., Beebe, K., Gordon, L., Sidransky, D., Liu, J. W., Schlegel, T., Payne, S., Hartmann, A., Latif, F. and Clark, G. J. 2010. The Ras effector RASSF2 controls the PAR-4 tumor suppressor. Mol. Cell. Biol. 30, 2608-2620.

상세보기
Downward, J. 2004. PI 3-kinase, Akt and cell survival. Semin. Cell Dev. Biol. 15, 177-182.

상세보기
El-Guendy, N. and Rangnekar, V. M. 2003. Apoptosis by Par-4 in cancer and neurodegenerative diseases. Exp. Cell Res. 283, 51-66.

상세보기
El-Guendy, N., Zhao, Y., Gurumurthy, S., Burikhanov, R. and Rangnekar, V. M. 2003. Identification of a unique core domain of par-4 sufficient for selective apoptosis induction in cancer cells. Mol. Cell. Biol. 23, 5516-5525.

상세보기
Goswami, A., Burikhanov, R., de Thonel, A., Fujita, N., Goswami, M., Zhao, Y., Eriksson, J. E., Tsuruo, T. and Rangnekar, V. M. 2005. Binding and phosphorylation of par-4 by akt is essential for cancer cell survival. Mol. Cell 20, 33-44.

상세보기
Gurumurthy, S., Goswami, A., Vasudevan, K. M. and Rangnekar, V. M. 2005. Phosphorylation of Par-4 by protein kinase A is critical for apoptosis. Mol. Cell. Biol. 25, 1146-1161.

상세보기
Jagtap, J. C., Dawood, P., Shah, R. D., Chandrika, G., Natesh, K., Shiras, A., Hegde, A. S., Ranade, D. and Shastry, P. 2014. Expression and regulation of prostate apoptosis response-4 (Par-4) in human glioma stem cells in drug-inducedapoptosis. PLoS One. 9, e88505.

상세보기
Jagtap, J. C., Parveen, D., Shah, R. D., Desai, A., Bhosale, D., Chugh, A., Ranade, D., Karnik, S., Khedkar, B., Mathur, A., Natesh, K., Chandrika, G. and Shastry, P. 2015. Secretory prostate apoptosis response (Par)-4 sensitizes multicellular spheroids (MCS) of glioblastoma multiforme cells to tamoxifen-inducedcell death. FEBS Open Bio. 5, 8-19.

상세보기
Johnstone, R. W., See, R. H., Sells, S. F., Wang, J., Muthukkumar, S., Englert, C., Haber, D. A., Licht, J. D., Sugrue, S. P., Roberts, T., Rangnekar, V. M. and Shi, Y. 1996. A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms’ tumor suppressor WT1. Mol. Cell. Biol. 16, 6945-6956.

상세보기
Johnstone, R. W., Tommerup, N., Hansen, C., Vissing, H. and Shi, Y. 1998. Mapping of the human PAWR (par-4) gene to chromosome 12q21. Genomics 53, 241-243.

상세보기
Kimura, M., Furukawa, T., Abe, T., Yatsuoka, T., Youssef, E. M., Yokoyama, T., Ouyang, H., Ohnishi, Y., Sunamura, M., Kobari, M., Matsuno, S. and Horii, A. 1998. Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer. Cancer Res. 58, 2456-2460.

상세보기
Kline, C. L. and Irby, R. B. 2011. The pro-apoptotic protein Prostate Apoptosis Response Protein-4 (Par-4) can be activated in colon cancer cells by treatment with Src inhibitor and 5-FU. Apoptosis 16, 1285-1294.

상세보기
Kogel, D., Plottner, O., Landsberg, G., Christian, S. and Scheidtmann, K. H. 1998. Cloning and characterization of Dlk, a novel serine/threonine kinase that is tightly associated with chromatin and phosphorylates core histones. Oncogene 17, 2645-2654.

상세보기
Kogel, D., Reimertz, C., Mech, P., Poppe, M., Fruhwald, M. C., Engemann, H., Scheidtmann, K. H. and Prehn, J. H. 2001. Dlk/ZIP kinase-induced apoptosis in human medulloblastoma cells: requirement of the mitochondrial apoptosis pathway. Br. J. Cancer 85, 1801-1808.

상세보기
Lee, A. S. 2009. The Par-4-GRP78 TRAIL, more twists and turns. Cancer Biol. Ther. 8, 2103-2105.

상세보기
Lee, T. J., Jang, J. H., Noh, H. J., Park, E. J., Choi, K. S. and Kwon, T. K. 2010. Overexpression of Par-4 sensitizes TRAIL-induced apoptosis via inactivation of NF-kappaB and Akt signaling pathways in renal cancer cells. J. Cell. Biochem. 109, 885-895.
Lee, T. J., Lee, J. T., Kim, S. H., Choi, Y. H., Song, K. S., Park, J. W. and Kwon, T. K. 2008. Overexpression of Par-4 enhances thapsigargin-induced apoptosis via down-regulation of XIAP and inactivation of Akt in human renal cancer cells. J. Cell. Biochem. 103, 358-368.

상세보기
Moreno-Bueno, G., Fernandez-Marcos, P. J., Collado, M., Tendero, M. J., Rodriguez-Pinilla, S. M., Garcia-Cao, I., Hardisson, D., Diaz-Meco, M. T., Moscat, J., Serrano, M. and Palacios, J. 2007. Inactivation of the candidate tumor suppressorpar-4 in endometrial cancer. Cancer Res. 67, 1927-1934.

상세보기
Nalca, A., Qiu, S. G., El-Guendy, N., Krishnan, S. and Rangnekar, V. M. 1999. Oncogenic Ras sensitizes cells to apoptosis by Par-4. J. Biol. Chem. 274, 29976-29983.

상세보기
Notaro, A., Sabella, S., Pellerito, O., Di Fiore, R., De Blasio, A., Vento, R., Calvaruso, G. and Giuliano, M. 2014. Involvement of PAR-4 in cannabinoid-dependent sensitization of osteosarcoma cells to TRAIL-induced apoptosis. Int. J. Biol. Sci. 10, 466-478.

상세보기
Pereira, M. C., de Bessa-Garcia, S. A., Burikhanov, R., Pavanelli, A. C., Antunes, L., Rangnekar, V. M. and Nagai, M. A. 2013. Prostate apoptosis response-4 is involved in the apoptosis response to docetaxel in MCF-7 breast cancer cells. Int. J. Oncol. 43, 531-538.

상세보기
Pruitt, K., Ulku, A. S., Frantz, K., Rojas, R. J., Muniz-Medina, V. M., Rangnekar, V. M., Der, C. J. and Shields, J. M. 2005. Ras-mediated loss of the pro-apoptotic response protein Par-4 is mediated by DNA hypermethylation through Raf-independent and Raf-dependent signaling cascades in epithelial cells. J. Biol. Chem. 280, 23363-23370.

상세보기
Qiu, G., Ahmed, M., Sells, S. F., Mohiuddin, M., Weinstein, M. H. and Rangnekar, V. M. 1999. Mutually exclusive expression patterns of Bcl-2 and Par-4 in human prostate tumors consistent with down-regulation of Bcl-2 by Par-4. Oncogene 18, 623-631.

상세보기
Rah, B., Amin, H., Yousuf, K., Khan, S., Jamwal, G., Mukherjee, D. and Goswami, A. 2012. A novel MMP-2 inhibitor 3-azidowithaferin A (3-azidoWA) abrogates cancer cell invasion and angiogenesis by modulating extracellular Par-4. PLoS One. 7, e44039.

상세보기
Rayet, B. and Gelinas, C. 1999. Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18, 6938-6947.

상세보기
Schneider, B. G., Rha, S. Y., Chung, H. C., Bravo, J. C., Mera, R., Torres, J. C., Plaisance, K. T. Jr., Schlegel, R., McBride, C. M., Reveles, X. T. and Leach, R. J. 2003. Regions of allelic imbalance in the distal portion of chromosome 12q in gastric cancer. Mol. Pathol. 56, 141-149.

상세보기
Schwarze, S. and Rangnekar, V. M. 2010. Targeting plasma membrane GRP78 for cancer growth inhibition. Cancer Biol. Ther. 9, 153-155.

상세보기
Sells, S. F., Wood, D. P. Jr., Joshi-Barve, S. S., Muthukumar, S., Jacob, R. J., Crist, S. A., Humphreys, S. and Rangnekar, V. M. 1994. Commonality of the gene programs induced by effectors of apoptosis in androgen-dependent and -independent prostate cells. Cell Growth Differ. 5, 457-466.
Srinivasan, S., Ranga, R. S., Burikhanov, R., Han, S. S. and Chendil, D. 2007. Par-4-dependent apoptosis by the dietary compound withaferin A in prostate cancer cells. Cancer Res. 67, 246-253.

상세보기
Szegezdi, E., Logue, S. E., Gorman, A. M. and Samali, A. 2006. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 7, 880-885.

상세보기
Thayyullathil, F., Pallichankandy, S., Rahman, A., Kizhakkayil, J., Chathoth, S., Patel, M. and Galadari, S. 2013. Caspase-3 mediated release of SAC domain containing fragment from Par-4 is necessary for the sphingosine-induced apoptosis in Jurkat cells. J. Mol. Signal. 8, 2.

상세보기
Thayyullathil, F., Rahman, A., Pallichankandy, S., Patel, M. and Galadari, S. 2014. ROS-dependent prostate apoptosis response-4 (Par-4) up-regulation and ceramide generation are the prime signaling events associated with curcumin-induced autophagic cell death in human malignant glioma. FEBS Open Bio. 4, 763-776.

상세보기
Zapata-Benavides, P., Mendez-Vazquez, J. L., GonzalezRocha, T. R., Zamora-Avila, D. E., Franco-Molina, M. A., Garza-Garza, R. and Rodriguez-Padilla, C. 2009. Expression of prostate apoptosis response (Par-4) is associated with progesterone receptor in breast cancer. Arch. Med. Res. 40, 595-599.

상세보기
Zhao, Y., Burikhanov, R., Qiu, S., Lele, S. M., Jennings, C. D., Bondada, S., Spear, B. and Rangnekar, V. M. 2007. Cancer resistance in transgenic mice expressing the SAC module of Par-4. Cancer Res. 67, 9276-9285.

상세보기
Zhao, Y. and Rangnekar, V. M. 2008. Apoptosis and tumor resistance conferred by Par-4. Cancer Biol. Ther. 7, 1867-1874.

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