Research Article
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Co-expression of P53 and P60-katanin shapes transcriptome dynamics

Year 2024, , 197 - 201, 15.10.2024
https://doi.org/10.23902/trkjnat.1521899

Abstract

Microtubules (MT), essential elements of the cytoskeleton have important roles in the cell such as intracellular cargo transport, cell motility and cell division. They provide support, growth and maintenance of the axonal and dendritic processes in neurons. Microtubule severing proteins such as katanin and spastin have roles in microtubule reconfiguration. Katanin is one of the best characterized severing proteins and is composed of catalytic subunit p60-katanin and regulatory subunit p80-katanin. The microtubule severing mechanism of p60-katanin has been depicted in detail, but how p60-katanin itself is regulated is still little-known. p53 is an important protein between proliferation and differentiation. It regulates different cellular mechanisms such as cell cycle arrest, senescence, differentiation, and apoptosis. p53 controls proliferation in dividing cells and is related to differentiation by means of affecting neuronal process length in non-dividing neurons. Both p53 and p60-katanin have critical roles in proliferation and differentiation separately. Moreover, these proteins were shown to physically interact, but their combined effect remains unclear. To this aim, the current study reveals the effects of p53 – p60-katanin co-expression on transcriptome of the fibroblast cells. Data indicated that the transcriptome of many different pathways such as actin regulation, neuroactive ligand-receptor interaction, and serotonergic synapses pathways were altered under p53 – p60-katanin co-expression conditions. Exploring combined effect of p53 and p60-katanin will help in design of new studies to better understand not only microtubule regulation but also neurodegenerative diseases that are linked to the reactivation of cell cycle and neuronal damage where two of these players take place.

Project Number

114Z971

References

  • 1. Baas, P.W. 1997. Microtubules and axonal growth. Current Opinion in Cell Biology, 9(1): 29-36. https://doi.org/10.1016/s0955-0674(97)80148-2
  • 2. Chen, Y. Rui, B.B., Tang, L.Y. & Hu, C.M. 2015. Lipin family proteins--key regulators in lipid metabolism. Annals of Nutrition and Metabolism, 66(1): 10-8. https://doi.org/10.1159/000368661
  • 3. Dai, C. & Lu, Y. 2004. Tumor suppressor p53 and its gain-of-function mutants in cancer. Acta Biochimica et Biophysica Sinica, 36(5): 283-293. https://doi.org/10.1093/abbs/gmt144
  • 4. de Cárcer, G., Escobar, B., Higuero, A. M., García, L., Ansón, A., Pérez, G. & Malumbres, M. 2011. PLK5, a Polo Box Domain-Only Protein with Specific Roles in Neuron Differentiation and Glioblastoma Suppression. Molecular and Cellular Biology, 31(6): 1225-1239. https://doi.org/10.1128/MCB.00607-10
  • 5. Di Giovanni, S., Knights, C.D., Rao, M., Yakovlev, A., Beers, J., Catania, J., Avantaggiati, M.L.& Faden, A.I. 2006. The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. European Molecular Biology Organization Journal, 25: 4084-4096. https://doi.org/10.1038/sj.emboj.7601292
  • 6. Duan, S., Cermak, L., Pagan, J.K., Rossi, M., Martinengo, C., di Celle, P.F. & Soucek, L. 2006. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature, 443(7111): 235-239.
  • 7. Ferreira, A. & Kosik, K.S. 1996. Accelerated neuronal differentiation induced by p53 suppression. Journal of Cell Science, 109: 1509-1516. https://doi.org/10.1002/stem.641
  • 8. Hayashi, T. & Karl Seder, J. 2013. DNA damage associated with mitosis and cytokinesis failure. Oncogene, 32(39): 4593-4601. https://doi.org/10.1038/onc.2012.615
  • 9. Hudson, C.D., Morris, P.J., Latchman, D.S. & Budhram-Mahadeo, V.S. 2005. Brn-3a transcription factor blocks p53-mediated activation of proapoptotic target genes Noxa and Bax in vitro and in vivo to determine cell fate. Journal of Biological Chemistry, 280: 11851-11858. https://doi.org/10.1074/jbc.M408679200
  • 10. Kim, J., Lengner, C.J., Kirak, O., Hanna, J., Cassady, J.P., Lodato, M.A., Wu, S., Faddah, D.A., Steine, E.J., Gao, Q., Fu, D., Dawlaty, M. & Jaenisch, R. 2011. Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors. Stem Cells, 29(6): 992-1000. https://doi.org/10.1002/stem.641
  • 11. Kırımtay, K., Selçuk, E., Kelle, D., Erman, B. & Karabay, A. 2020. p53 regulates katanin-p60 promoter in HCT 116 cells. Gene, 727: 144241. https://doi.org/10.1016/j.gene.2019.144241
  • 12. Korulu, S. & Yildiz, A. 2020. p60-katanin: a novel interacting partner for p53. Molecular Biology Reports, 47: 4295-4301. https://doi.org/10.1007/s11033-020-05557-6
  • 13. Lane, D.P. 1992. Cancer. p53, guardian of the genome. Nature, 358(6381): 15-16. https://doi.org/10.1038/358015a0
  • 14. Lombino, F. L., Muhia, M., Lopez-Rojas, J., Brill, M. S., Thies, E., Ruschkies, L., Lutz, D., Richter, M., Hausrat, T. J., Lopes, A. T., McNally, F. J., Hermans-Borgmeyer, I., Dunleavy, J. E. M., Hoffmeister-Ullerich, S., Frotscher, M., Misgeld, T., Kreutz, M. R., de Anda, F. C. & Kneussel, M. 2019. The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis. Scietific Reports, 9: 15940. https://doi.org/10.1038/s41598-019-52367-3
  • 15. McNally, F.J. & Vale, R.D. 1993 Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell, 75(3): 419-429. https://doi.org/10.1016/0092-8674(93)90377-3
  • 16. McNally, F.J. 2013. Mechanisms of spindle positioning. Journal of Cell Biology, 200(2): 131-140. https://doi.org/10.1083/jcb.201210007
  • 17. Parfenyev, S., Singh, A., Fedorova, O. Daks, A., Kulshreshtha, R., Barlev, N. A. 2021. Interplay between p53 and non-coding RNAs in the regulation of EMT in breast cancer. Cell Death and Disease, 12: 17. https://doi.org/10.1038/s41419-020-03327-7
  • 18. Piccini, A., Castroflorio, E., Valente, P., Guarnieri, F. C., Aprile, D., Michetti, C., Bramini, M., Giansante, G., Pinto, B., Savardi, A., Cesca, F., Bachi, A., Cattaneo, A., Wren, J. D., Fassio, A., Valtorta, F., Benfenati, F. & Giovedì, S. 2017. APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development. Cell reports, 21(12): 3596-3611. https://doi.org/10.1016/j.celrep.2017.11.073
  • 19. Su, S., Ndiaye, M.A., Guzmán-Pérez, G., Baus, R.M., Huang, W., Patankar, M.S. & Ahmad, N. 2023. Potential Tumor Suppressor Role of Polo-like Kinase 5 in Cancer. Cancers, 15(22): 5457. https://doi.org/10.3390/cancers15225457
  • 20. Umair, M., Ballow, M., Asiri, A., Alyafee. Y., Al Tuwaijri, A., Alhamoudi, K.M., Aloraini, T., Abdelhakim, M., Althagafi, A.T., Kafkas, S., Alsubaie, L., Alrifai, M.T., Hoehndorf, R., Alfares, A. & Alfadhel, M. 2020. EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay. Clinical Genetics. 98(6): 555-561. https://doi.org/10.1111%2Fcge.13842
  • 21. Vousden, K.H. & Prives, C. 2009. Blinded by the light: The growing complexity of p53. Cell, 137(3): 413-431. https://doi.org/10.1016/j.cell.2009.04.037
  • 22. Yang, Z., Wan, J., Ma, L., Li, Z., Yang, R., Yang, H., Li, J., Zhou, F. & Ming, L. 2023. Long non-coding RNA HOXC-AS1 exerts its oncogenic effects in esophageal squamous cell carcinoma by interaction with IGF2BP2 to stabilize SIRT1 expression. Journal of clinical laboratory analysis, 37(1): e24801. https://doi.org/10.1002/jcla.24801
  • 23. Zhang, R., Gao, K., Sadremomtaz, A., Ruiz-Moreno, A.J., Monti, A., Al-Dahmani, Z.M, Gyau, B.B., Doti, N. & Groves, M.R. 2023. Identification of hotspots in synthetic peptide inhibitors of the FOXO4:p53 interaction. Gene & Protein in Disease, 2(3): 1491. https://doi.org/10.36922/gpd.1491
Year 2024, , 197 - 201, 15.10.2024
https://doi.org/10.23902/trkjnat.1521899

Abstract

Mikrotübüller (MT), hücre iskeletinin temel elemanları olup hücre içi kargo taşınması, hücre hareketliliği ve hücre bölünmesi gibi hücrede önemli rollere sahiptir. Ayrıca sinir hücreleri olan nöronlarda, aksonal ve dendritik yapıların desteklenmesi ve uzaması için önemli görevlere sahiptirler. Katanin ve spastin gibi mikrotübül kesici proteinler, mikrotübüllerin yeniden yapılandırılmasında rol oynar. Katanin, en iyi karakterize edilmiş MT kesici proteinlerden olup, katalitik alt birim p60-katanin ve düzenleyici alt birim p80-katanin'den oluşur. p60-katanin'in mikrotübül kesme mekanizması oldukça iyi bilinmektedir, ancak p60-katanin'in kendisinin nasıl düzenlendiği halen az bilinen bir konudur. p53, proliferasyon ve farklılaşma arasında kritik bir proteindir. Hücre döngüsünü, yaşlanma, farklılaşma ve apoptoz gibi farklı hücresel mekanizmaları düzenler. p53'ün bölünen hücrelerde proliferasyonu kontrol ettiği, bölünmeyen nöronlarda ise farklılaşma ile ilişkili olduğu ortaya konmuştur. Hem p60-katanin hem de p53, ayrı ayrı proliferasyon ve farklılaşmada kritik rollere sahiptir. Ayrıca, bu proteinlerin fiziksel olarak etkileşimde bulunduğu da gösterilmiştir, ancak bu proteinlerin birleşik etkisi belirsizliğini korumaktadır. Bu amaçla, mevcut çalışma, p53 ve p60-katanin’in birlikte eksprese edilmesinin fibroblast hücrelerinin transkriptomu üzerindeki etkilerini ortaya koymaktadır. Veriler, aktin düzenlenmesi, nöroaktif ligand-reseptör etkileşimi, serotonerjik sinaps yolları gibi birçok farklı yolakların transkriptomlarının p53 – p60-katanin’in birlikte ekprese edildiğinde değiştiğini göstermiştir. p53 ve p60-katanin'in birleşik etkisinin araştırılması, sadece mikrotübül düzenlemesini daha iyi anlamak için değil, aynı zamanda bu iki proteinin rol oynadığı hücre bölünmesinin yeniden aktifleşmesi ve nöronal hasarla ilişkili nörodejeneratif hastalıkları daha iyi anlamak için yeni çalışmaların tasarlanmasına da öncülük edecektir.

Project Number

114Z971

References

  • 1. Baas, P.W. 1997. Microtubules and axonal growth. Current Opinion in Cell Biology, 9(1): 29-36. https://doi.org/10.1016/s0955-0674(97)80148-2
  • 2. Chen, Y. Rui, B.B., Tang, L.Y. & Hu, C.M. 2015. Lipin family proteins--key regulators in lipid metabolism. Annals of Nutrition and Metabolism, 66(1): 10-8. https://doi.org/10.1159/000368661
  • 3. Dai, C. & Lu, Y. 2004. Tumor suppressor p53 and its gain-of-function mutants in cancer. Acta Biochimica et Biophysica Sinica, 36(5): 283-293. https://doi.org/10.1093/abbs/gmt144
  • 4. de Cárcer, G., Escobar, B., Higuero, A. M., García, L., Ansón, A., Pérez, G. & Malumbres, M. 2011. PLK5, a Polo Box Domain-Only Protein with Specific Roles in Neuron Differentiation and Glioblastoma Suppression. Molecular and Cellular Biology, 31(6): 1225-1239. https://doi.org/10.1128/MCB.00607-10
  • 5. Di Giovanni, S., Knights, C.D., Rao, M., Yakovlev, A., Beers, J., Catania, J., Avantaggiati, M.L.& Faden, A.I. 2006. The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. European Molecular Biology Organization Journal, 25: 4084-4096. https://doi.org/10.1038/sj.emboj.7601292
  • 6. Duan, S., Cermak, L., Pagan, J.K., Rossi, M., Martinengo, C., di Celle, P.F. & Soucek, L. 2006. FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature, 443(7111): 235-239.
  • 7. Ferreira, A. & Kosik, K.S. 1996. Accelerated neuronal differentiation induced by p53 suppression. Journal of Cell Science, 109: 1509-1516. https://doi.org/10.1002/stem.641
  • 8. Hayashi, T. & Karl Seder, J. 2013. DNA damage associated with mitosis and cytokinesis failure. Oncogene, 32(39): 4593-4601. https://doi.org/10.1038/onc.2012.615
  • 9. Hudson, C.D., Morris, P.J., Latchman, D.S. & Budhram-Mahadeo, V.S. 2005. Brn-3a transcription factor blocks p53-mediated activation of proapoptotic target genes Noxa and Bax in vitro and in vivo to determine cell fate. Journal of Biological Chemistry, 280: 11851-11858. https://doi.org/10.1074/jbc.M408679200
  • 10. Kim, J., Lengner, C.J., Kirak, O., Hanna, J., Cassady, J.P., Lodato, M.A., Wu, S., Faddah, D.A., Steine, E.J., Gao, Q., Fu, D., Dawlaty, M. & Jaenisch, R. 2011. Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors. Stem Cells, 29(6): 992-1000. https://doi.org/10.1002/stem.641
  • 11. Kırımtay, K., Selçuk, E., Kelle, D., Erman, B. & Karabay, A. 2020. p53 regulates katanin-p60 promoter in HCT 116 cells. Gene, 727: 144241. https://doi.org/10.1016/j.gene.2019.144241
  • 12. Korulu, S. & Yildiz, A. 2020. p60-katanin: a novel interacting partner for p53. Molecular Biology Reports, 47: 4295-4301. https://doi.org/10.1007/s11033-020-05557-6
  • 13. Lane, D.P. 1992. Cancer. p53, guardian of the genome. Nature, 358(6381): 15-16. https://doi.org/10.1038/358015a0
  • 14. Lombino, F. L., Muhia, M., Lopez-Rojas, J., Brill, M. S., Thies, E., Ruschkies, L., Lutz, D., Richter, M., Hausrat, T. J., Lopes, A. T., McNally, F. J., Hermans-Borgmeyer, I., Dunleavy, J. E. M., Hoffmeister-Ullerich, S., Frotscher, M., Misgeld, T., Kreutz, M. R., de Anda, F. C. & Kneussel, M. 2019. The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis. Scietific Reports, 9: 15940. https://doi.org/10.1038/s41598-019-52367-3
  • 15. McNally, F.J. & Vale, R.D. 1993 Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell, 75(3): 419-429. https://doi.org/10.1016/0092-8674(93)90377-3
  • 16. McNally, F.J. 2013. Mechanisms of spindle positioning. Journal of Cell Biology, 200(2): 131-140. https://doi.org/10.1083/jcb.201210007
  • 17. Parfenyev, S., Singh, A., Fedorova, O. Daks, A., Kulshreshtha, R., Barlev, N. A. 2021. Interplay between p53 and non-coding RNAs in the regulation of EMT in breast cancer. Cell Death and Disease, 12: 17. https://doi.org/10.1038/s41419-020-03327-7
  • 18. Piccini, A., Castroflorio, E., Valente, P., Guarnieri, F. C., Aprile, D., Michetti, C., Bramini, M., Giansante, G., Pinto, B., Savardi, A., Cesca, F., Bachi, A., Cattaneo, A., Wren, J. D., Fassio, A., Valtorta, F., Benfenati, F. & Giovedì, S. 2017. APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development. Cell reports, 21(12): 3596-3611. https://doi.org/10.1016/j.celrep.2017.11.073
  • 19. Su, S., Ndiaye, M.A., Guzmán-Pérez, G., Baus, R.M., Huang, W., Patankar, M.S. & Ahmad, N. 2023. Potential Tumor Suppressor Role of Polo-like Kinase 5 in Cancer. Cancers, 15(22): 5457. https://doi.org/10.3390/cancers15225457
  • 20. Umair, M., Ballow, M., Asiri, A., Alyafee. Y., Al Tuwaijri, A., Alhamoudi, K.M., Aloraini, T., Abdelhakim, M., Althagafi, A.T., Kafkas, S., Alsubaie, L., Alrifai, M.T., Hoehndorf, R., Alfares, A. & Alfadhel, M. 2020. EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay. Clinical Genetics. 98(6): 555-561. https://doi.org/10.1111%2Fcge.13842
  • 21. Vousden, K.H. & Prives, C. 2009. Blinded by the light: The growing complexity of p53. Cell, 137(3): 413-431. https://doi.org/10.1016/j.cell.2009.04.037
  • 22. Yang, Z., Wan, J., Ma, L., Li, Z., Yang, R., Yang, H., Li, J., Zhou, F. & Ming, L. 2023. Long non-coding RNA HOXC-AS1 exerts its oncogenic effects in esophageal squamous cell carcinoma by interaction with IGF2BP2 to stabilize SIRT1 expression. Journal of clinical laboratory analysis, 37(1): e24801. https://doi.org/10.1002/jcla.24801
  • 23. Zhang, R., Gao, K., Sadremomtaz, A., Ruiz-Moreno, A.J., Monti, A., Al-Dahmani, Z.M, Gyau, B.B., Doti, N. & Groves, M.R. 2023. Identification of hotspots in synthetic peptide inhibitors of the FOXO4:p53 interaction. Gene & Protein in Disease, 2(3): 1491. https://doi.org/10.36922/gpd.1491
There are 23 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other), Animal Cell and Molecular Biology
Journal Section Research Article/Araştırma Makalesi
Authors

Şirin Korulu 0000-0001-6762-0659

Project Number 114Z971
Publication Date October 15, 2024
Submission Date July 24, 2024
Acceptance Date October 11, 2024
Published in Issue Year 2024

Cite

APA Korulu, Ş. (2024). Co-expression of P53 and P60-katanin shapes transcriptome dynamics. Trakya University Journal of Natural Sciences, 25(2), 197-201. https://doi.org/10.23902/trkjnat.1521899
AMA Korulu Ş. Co-expression of P53 and P60-katanin shapes transcriptome dynamics. Trakya Univ J Nat Sci. October 2024;25(2):197-201. doi:10.23902/trkjnat.1521899
Chicago Korulu, Şirin. “Co-Expression of P53 and P60-Katanin Shapes Transcriptome Dynamics”. Trakya University Journal of Natural Sciences 25, no. 2 (October 2024): 197-201. https://doi.org/10.23902/trkjnat.1521899.
EndNote Korulu Ş (October 1, 2024) Co-expression of P53 and P60-katanin shapes transcriptome dynamics. Trakya University Journal of Natural Sciences 25 2 197–201.
IEEE Ş. Korulu, “Co-expression of P53 and P60-katanin shapes transcriptome dynamics”, Trakya Univ J Nat Sci, vol. 25, no. 2, pp. 197–201, 2024, doi: 10.23902/trkjnat.1521899.
ISNAD Korulu, Şirin. “Co-Expression of P53 and P60-Katanin Shapes Transcriptome Dynamics”. Trakya University Journal of Natural Sciences 25/2 (October 2024), 197-201. https://doi.org/10.23902/trkjnat.1521899.
JAMA Korulu Ş. Co-expression of P53 and P60-katanin shapes transcriptome dynamics. Trakya Univ J Nat Sci. 2024;25:197–201.
MLA Korulu, Şirin. “Co-Expression of P53 and P60-Katanin Shapes Transcriptome Dynamics”. Trakya University Journal of Natural Sciences, vol. 25, no. 2, 2024, pp. 197-01, doi:10.23902/trkjnat.1521899.
Vancouver Korulu Ş. Co-expression of P53 and P60-katanin shapes transcriptome dynamics. Trakya Univ J Nat Sci. 2024;25(2):197-201.

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