International Journal of Innovative Approaches in Science Research
Abbreviation: IJIASR | ISSN (Print): 2602-4810 | ISSN (Online): 2602-4535 | DOI: 10.29329/ijiasr

Review article    |    Open Access
International Journal of Innovative Approaches in Science Research 2019, Vol. 3(3) 83-97

'DNA Hasarı Yanıtı'nın İnce Ayarında PPM1D/Wip1 Fosfataz'ın Rolü

Mehtap Kılıç Eren & Nur Betül Kartal

pp. 83 - 97   |  DOI: https://doi.org/10.29329/ijiasr.2019.213.2

Published online: October 20, 2019  |   Number of Views: 165  |  Number of Download: 916

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Abstract

Sağlıklı hücreler genom bütünlüğünü, hücre döngüsündeki ilerleyişi erteleyen/durduran ve DNA tamirini devreye sokan korunmuş bir DNA hasarı yanıtı yolağını aktive ederek sürdürürler. Bu sinyal yolağının düzgün olarak çalışmasını engelleyen moleküler bozukluklar genellikle kansere yatkınlık kazandırırlar. DNA hasarı yanıtı (DDR), hücreleri genomik kararsızlıktan korur ve kanser gelişimini önler.

DNA hasarının moduna ve seviyesine bağlı olarak, DDR sinyal ağı hücre döngüsünün geçici durdurulmasını (kontrol noktası), kalıcı büyümenin durdurulmasını (yaşlanma, senesens) veya programlanmış hücre ölümünü (apoptozis) teşvik eder. DDR'ye katılan proteinleri kodlayan genler tipik olarak tümör baskılayıcılardır ve yaygın olarak kanserde mutasyona uğrarlar. DDR yolağı temel olarak proteinlerin fosforilasyon ve defosforilasyonlarını kapsayan bir mekanizma ile düzenlenir.

Yabanıl tip p53 ile indüklenen fosfataz veya (Wild-type p53-inducible phosphatase (Wip1)), veya protein fosfataz tip 2C delta (protein phosphatase type 2C delta (PPM1D)) olarak da bilinen Wip1, DDR’ ın merkezinde yer alan ve önemli tümör baskılayıcıları hedef alan bir onko-proteindir. Bu derleme de, DDR’nin ince ayarında Wip1 aktivitesinin rolü ve bir onkogen olarak apoptozis ve senesens gibi hücresel stres yanıtları üzerine etkileri tartışılmıştır.

Keywords: DNA hasarı yanıtı, PPM1D / Wip1, p53, apoptoz, yaşlanma

How to Cite this Article

APA 6th edition
Eren, M.K. & Kartal, N.B. (2019). 'DNA Hasarı Yanıtı'nın İnce Ayarında PPM1D/Wip1 Fosfataz'ın Rolü . International Journal of Innovative Approaches in Science Research, 3(3), 83-97. doi: 10.29329/ijiasr.2019.213.2

Harvard
Eren, M. and Kartal, N. (2019). 'DNA Hasarı Yanıtı'nın İnce Ayarında PPM1D/Wip1 Fosfataz'ın Rolü . International Journal of Innovative Approaches in Science Research, 3(3), pp. 83-97.

Chicago 16th edition
Eren, Mehtap Kilic and Nur Betul Kartal (2019). "'DNA Hasarı Yanıtı'nın İnce Ayarında PPM1D/Wip1 Fosfataz'ın Rolü ". International Journal of Innovative Approaches in Science Research 3 (3):83-97. doi:10.29329/ijiasr.2019.213.2.
References
  1. Bartek, J. Lukas, J. Bartkova, J. 2007. "DNA damage response as an anti-cancer barrier: damage threshold and the concept of 'conditional haploinsufficiency'". Cell cycle 6: 2344-2347. [Google Scholar]
  2. Bartek, J. Lukas, J. 2007. "DNA damage checkpoints: from initiation to recovery or adaptation". Current opinion in cell biology 19: 238-245. [Google Scholar]
  3. Bartkova, J. Rezaei, N. Liontos, M. Karakaidos, P. Kletsas, D. Issaeva, N. Vassiliou, LV. Kolettas, E. Niforou, K. Zoumpourlis, VC. et al. 2006. "Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints". Nature 444: 633-637. [Google Scholar]
  4. Bulavin, DV. Demidov, ON. Saito, S. Kauraniemi, P. Phillips, C. Amundson, SA. Ambrosino, C. Sauter, G. Nebreda, AR. Anderson, CW. et al. 2002. "Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity". Nature genetics 31: 210-215. [Google Scholar]
  5. Bulavin. DV. Phillips, C. Nannenga, B. Timofeev, O. Donehower, LA. Anderson, CW. Appella, E. Fornace, AJ. 2004. "Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway". Nature genetics 36: 343-350. [Google Scholar]
  6. Buss MC, Read TA, Schniederjan MJ, Gandhi K and Castellino RC. 2012. “HDM2 promotes Wip1‑mediated medulloblastoma growth”. Neuro Oncol 14: 440‑458,  [Google Scholar]
  7. Castellino, RC. De Bortoli, M. Lu, X. Moon, SH. Nguyen, TA. Shepard, MA. Rao, PH. Donehower, LA. Kim, JY. 2008. "Medulloblastomas overexpress the p53-inactivating oncogene WIP1/PPM1D". Journal of neuro-oncology 86: 245-256. [Google Scholar]
  8. Chew, J. Biswas, S. Shreeram, S. Humaidi, M. Wong, ET. Dhillion, MK. Teo, H. Hazra, A. Fang, CC. Lopez-Collazo, E. et al. 2009. "WIP1 phosphatase is a negative regulator of NF-kappaB signalling". Nature cell biology 11: 659-666. [Google Scholar]
  9. Choi, J. Appella, E. Donehower, LA. 2000. "The structure and expression of the murine wildtype p53-induced phosphatase 1 (Wip1) gene". Genomics 64: 298-306. [Google Scholar]
  10. Choi, J. Nannenga, B. Demidov, ON. Bulavin, DV. Cooney, A. Brayton, C. Zhang, Y. Mbawuike, IN. Bradley, A. Appella, E. et al. 2002. "Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control". Molecular and cellular biology 22: 1094-1105. [Google Scholar]
  11. Clausse V, Goloudina AR, Uyanik B, Kochetkova EY, Richaud S, Fedorova OA, Hammann A, Bardou M, Barlev NA, Garrido C et al. 2016. "Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy". Cell death & disease 7: e2195. [Google Scholar]
  12. Crescenzi, E. Raia, Z. Pacifico, F. Mellone, S. Moscato, F. Palumbo, G. Leonardi, A. 2013. "Down-regulation of wild-type p53-induced phosphatase 1 (Wip1) plays a critical role in regulating several p53-dependent functions in premature senescent tumor cells". The Journal of biological chemistry 288: 16212-16224. [Google Scholar]
  13. Feng, Z. Hu, W. Stanchina, E. Teresky, AK. Jin, S. Lowe, S. Levine, AJ. 2007, ‘The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways’. Cancer research, 3043–3053.  [Google Scholar]
  14. Fiscella, M. Zhang, H. Fan, S. Sakaguchi, K. Shen, S. Mercer, WE. Vande Woude, GF. O'Connor, PM. Appella, E. 1997. "Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner". Proceedings of the National Academy of Sciences of the United States of America 94: 6048-6053. [Google Scholar]
  15. Fuku, T. Semba, S. Yutori, H. Yokozaki, H. 2007. "Increased wild-type p53-induced phosphatase 1 (Wip1 or PPM1D) expression correlated with downregulation of checkpoint kinase 2 in human gastric carcinoma". Pathology international 57: 566-571. [Google Scholar]
  16. Gilmartin, AG. Faitg, TH. Richter, M. Groy, A. Seefeld, MA. Darcy, MG. Peng, X. Federowicz, K, Yang, J. Zhang, SY. et al. 2014. "Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction". Nature chemical biology 10: 181-187. [Google Scholar]
  17. Goloudina AR, Kochetkova EY, Pospelova TV, Demidov ON. 2016. "Wip1 phosphatase: between p53 and MAPK kinases pathways". Oncotarget 7: 31563-31571. [Google Scholar]
  18. Goloudina AR, Mazur SJ, Appella E, Garrido C, Demidov ON. 2012a. "Wip1 sensitizes p53-negative tumors to apoptosis by regulating the Bax/Bcl-xL ratio". Cell cycle 11: 1883-1887. [Google Scholar]
  19. Goloudina AR, Tanoue K, Hammann A, Fourmaux E, Le Guezennec X, Bulavin DV, Mazur SJ, Appella E, Garrido C, Demidov ON. 2012b. "Wip1 promotes RUNX2-dependent apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents". Proceedings of the National Academy of Sciences of the United States of America 109: E68-75. [Google Scholar]
  20. Halazonetis, TD. Gorgoulis, VG. Bartek, J. 2008, ‘An oncogene-induced DNA damage model for cancer development’.  Science 319 (5868):1352-5. [Google Scholar]
  21. Hershko, T. Korotayev, K. Polager, S. Ginsberg, D. 2006. "E2F1 modulates p38 MAPK phosphorylation via transcriptional regulation of ASK1 and Wip1". The Journal of biological chemistry 281: 31309-31316. [Google Scholar]
  22. Hu Feng W., Modica Z., Klimstra I., Song DS., Allen L., Brennan PJ., Levine MF., Tang AJ., LH. 2010. "Gene Amplifications in Well-Differentiated Pancreatic Neuroendocrine Tumors Inactivate the p53 Pathway". Genes & cancer 1: 360-368. [Google Scholar]
  23. Jackson, SP. Bartek, J. 2009, ‘The DNA-damage response in human biology and disease’. Nature, 461:1071-8. [Google Scholar]
  24. Kilic Eren, M. Tabor, V. 2014. "The role of hypoxia inducible factor-1 alpha in bypassing oncogene-induced senescence". PloS one 9: e101064. [Google Scholar]
  25. Kilic, M. Schmitt, CA. 2008.  Tumor senescence in cancer treatment. Part 6. Chapter III. "Exploiting drug induced senescence in transgenic mouse models" BEYOND APOPTOSIS: CELLULAR OUTCOMES OF CANCER THERAPY,. in Book "  Tumor senescence in cancer treatment. Part 6. Chapter III. "Exploiting drug induced senescence in transgenic mouse models" BEYOND APOPTOSIS: CELLULAR OUTCOMES OF CANCER THERAPY," p. 273. Informa Health Care USA, New York. [Google Scholar]
  26. Kleiblova, P. Shaltiel, A. Benada, J. Sevcik, J. Pechackova, S. Pohlreich, P. Voest, EE. Dundr, P. Bartek, J. Kleibl, Z. et al. 2013. "Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint". The Journal of cell biology 201: 511-521. [Google Scholar]
  27. Lee, J. S., Lee, M. O., Moon, B. H., Shim, S. H., Fornace Jr, A. J., & Cha, H. J. (2009). Senescent growth arrest in mesenchymal stem cells is bypassed by Wip1‐mediated downregulation of intrinsic stress signaling pathways. Stem cells, 27(8), 1963-1975. [Google Scholar]
  28. Le Guezennec, X. Bulavin, DV. 2010. "WIP1 phosphatase at the crossroads of cancer and aging". Trends in biochemical sciences 35: 109-114. [Google Scholar]
  29. Le Guezennec, X. Brichkina, A. Huang, YF. Kostromina, E. Han, W. Bulavin, DV. 2012, ‘Wip1-dependent regulation of autophagy, obesity, and atherosclerosis’. Cell Metab, 16 (1):68-8. [Google Scholar]
  30. Lieber, M. R. (2010). The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annual review of biochemistry, 79, 181-211. [Google Scholar]
  31. Lindqvist, A. de Bruijn, M. Macurek, L. Bras, A. Mensinga, A. Bruinsma, W. Voets, O. Kranenburg, O. Medema, RH. 2009. "Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression". The EMBO journal 28: 3196-3206. [Google Scholar]
  32. Loukopoulos, P., Shibata, T., Katoh, H., Kokubu, A., Sakamoto, M., Yamazaki, K., ... & Ohki, M. (2007). Genome‐wide array‐based comparative genomic hybridization analysis of pancreatic adenocarcinoma: identification of genetic indicators that predict patient outcome. Cancer science, 98(3), 392-400. [Google Scholar]
  33. Lowe, J. Cha, H. Lee, MO. Mazur, SJ. Appella, E. Fornace, AJ.  2012. "Regulation of the Wip1 phosphatase and its effects on the stress response". Frontiers in bioscience 17: 1480-1498. [Google Scholar]
  34. Lu, X. Ma, O. Nguyen, TA. Jones, SN. Oren, M. Donehower, LA. 2007. "The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop". Cancer cell 12: 342-354. [Google Scholar]
  35. Lu, X. Nguyen, TA. Moon, SH. Darlington, Y. Sommer, M. Donehower, LA. 2008. "The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways". Cancer metastasis reviews 27: 123-135. [Google Scholar]
  36. Lukas, J. Lukas, C. Bartek, J. 2011,’ More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance’. Nat Cell Biology., 13(10):1161-9 [Google Scholar]
  37. Macurek L, Benada J, Mullers E, Halim VA, Krejcikova K, Burdova K, Pechackova S, Hodny Z, Lindqvist A, Medema RH et al. 2013. "Downregulation of Wip1 phosphatase modulates the cellular threshold of DNA damage signaling in mitosis". Cell cycle 12: 251-262. [Google Scholar]
  38. Medema, RH. Macurek, L. 2012. "Checkpoint control and cancer". Oncogene 31: 2601-2613. [Google Scholar]
  39. Mirzayans, R. Andrais, B. Scott, A. Wang, YW. Murray, D. 2013. "Ionizing radiation-induced responses in human cells with differing TP53 status". International journal of molecular sciences 14: 22409-22435. [Google Scholar]
  40. Oliva-Trastoy, M. Berthonaud, V. Chevalier, A. Ducrot, C. Marsolier-Kergoat, MC. Mann, C. Leteurtre, F. 2007. "The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase". Oncogene 26: 1449-1458. [Google Scholar]
  41. Parssinen J, Alarmo EL, Khan S, Karhu R, Vihinen M, Kallioniemi A. 2008. "Identification of differentially expressed genes after PPM1D silencing in breast cancer". Cancer letters 259: 61-70. [Google Scholar]
  42. Pecháčková, S. Burdová, K. Macurek, L. 2017, ‘WIP1 phosphatase as pharmacological target in cancer therapy’. J Mol Med. 589–599. [Google Scholar]
  43. Pechackova S, Burdova K, Benada J, Kleiblova P, Jenikova G, Macurek L. 2016. "Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3". Oncotarget 7: 14458-14475. [Google Scholar]
  44. Rauta, J. Alarmo, EL. Kauraniemi, P. Karhu, R. Kuukasjarvi, T. Kallioniemi, A. 2006. "The serine-threonine protein phosphatase PPM1D is frequently activated through amplification in aggressive primary breast tumours". Breast cancer research and treatment 95: 257-263. [Google Scholar]
  45. Roos, WP.Thomas, AD. Kaina, B, 2016,’ DNA damage and the balance between survival and death in cancer biology’. Nat Rev Cancer.,16(1):20-33. [Google Scholar]
  46. Ruark E, Snape K, Humburg P, Loveday C, Bajrami I, Brough R, Rodrigues DN, Renwick A, Seal S, Ramsay E et al. 2013. "Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer". Nature 493: 406-410. [Google Scholar]
  47. Saito-Ohara, F. Imoto I. Inoue, J. Hosoi, H. Nakagawara, A. Sugimoto, T. Inazawa J. 2003. "PPM1D is a potential target for 17q gain in neuroblastoma". Cancer research 63: 1876-1883. [Google Scholar]
  48. Schreiber, V., Amé, J. C., Dollé, P., Schultz, I., Rinaldi, B., Fraulob, V., ... & de Murcia, G. (2002). Poly (ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. Journal of Biological Chemistry, 277(25), 23028-23036. [Google Scholar]
  49. Shreeram, S. Hee, WK. Demidov, ON. Kek, C. Yamaguchi, H. Fornace, AJ. Anderson, CW. Appella, E. Bulavin, DV. 2006. "Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase". The Journal of experimental medicine 203: 2793-2799. [Google Scholar]
  50. Song, JY. Ryu, SH. Cho, YM. Kim, YS. Lee, BM. Lee, SW. Choi, J. 2013. "Wip1 suppresses apoptotic cell death through direct dephosphorylation of BAX in response to gamma-radiation". Cell death & disease 4: e744. [Google Scholar]
  51. Takekawa, M. Adachi, M. Nakahata, A. Nakayama, I. Itoh, F. Tsukuda, H. Taya, Y. Imai, K. 2000. "P53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation". The EMBO journal 19: 6517-6526. [Google Scholar]
  52. Tan, DS. Lambros, MB. Rayter, S. Natrajan, R. Vatcheva, R. Gao, Q. Marchio, C. Geyer, FC. Savage, K. Parry, S. et al. 2009. "PPM1D is a potential therapeutic target in ovarian clear cell carcinomas". Clinical Cancer Research 15: 2269-2280. [Google Scholar]
  53. Uyanik B, Grigorash BB, Goloudina AR, Demidov ON. 2017. "DNA damage-induced phosphatase Wip1 in regulation of hematopoiesis, immune system and inflammation". Cell death discovery 3: 17018 [Google Scholar]
  54. Xia, Y. Ongusaha, P. Lee, SW. Liou, YC. 2009. "Loss of Wip1 sensitizes cells to stress- and DNA damage-induced apoptosis". The Journal of biological chemistry 284: 17428-17437. [Google Scholar]
  55. Yang DH, He JA, Li J, Ma WF, Hu XH, Xin SJ, Duan ZQ. 2017.  "[Expression of proto-oncogene Wip1 in breast cancer and its clinical significance]". Molecular medicine report 15 (2): 519-522. [Google Scholar]
  56. Yu, E. Ahn, YS. Jang, SJ. Kim, MJ. Yoon, HS. Gong, G. Choi, J. 2007. "Overexpression of the wip1 gene abrogates the p38 MAPK/p53/Wip1 pathway and silences p16 expression in human breast cancers". Breast cancer research and treatment 101: 269-278. [Google Scholar]
  57. Zhang, X. Wan, G. Mlotshwa, S. Vance, V. Berger, FG. Chen, H. Lu, X. 2010. "Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway". Cancer research 70: 7176-7186. [Google Scholar]
  58. Zhang L, Chen LH, Wan H, Yang R, Wang Z, Feng J, Yang S, Jones S, Wang S, Zhou W. 2014. “Exome sequencing identifies somatic gain‑of‑function PPM1D mutations in brainstem gliomas”. Nat Genet 46: 726‑730,. [Google Scholar]
  59. Zhu, YH. Bulavin, DV. 2012. "Wip1-dependent signaling pathways in health and diseases". Progress in molecular biology and translational science 106: 307-325. [Google Scholar]
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