Skip to main content

Advertisement

SpringerLink
Log in

p60-katanin: a novel interacting partner for p53

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Katanin, one of the best-characterized microtubule (MT) severing proteins, is composed of two subunits: catalytic p60-katanin, and regulatory p80-katanin. p60-katanin triggers MT reorganization by severing them. MT reorganization is essential for both mitotic cells and post-mitotic neurons in numerous vital processes such as intracellular transport, mitosis, cellular differentiation and apoptosis. Due to the deleterious effect of continuous severing for cells, p60-katanin requires a strategic regulation. However, there are only a few known regulators of p60-katanin. p53 functions in similar cellular processes as katanin such as cell cycle, differentiation, and apoptosis depending on its interacting partners. Considering this similarity, in this study we investigated p53 as a potential regulatory candidate of p60-katanin, and examined their interaction. Co-immunoprecipitation analyses revealed that p60-katanin interacts with p53. We were able to locate a potential interaction site for the two proteins by deleting different candidate regions We showed for the first time that p53 and p60-katanin interact. This interaction appears to occur via p53’s DNA binding domain and p60-katanin’s C-terminal. This study will pave the way for future studies regarding the functional outcomes of this interaction which is vital for understanding the regulation of cellular events such as cell cycle, differentiation, and apoptosis in disease and in health.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

taken from https://www.rcsb.org/ for p60-katanin (5ZQL, crystal structure of human katanin AAA ATPase domain) and p53 (2FEJ, solution structure of human p53 DNA binding domain)

Similar content being viewed by others

References

  1. McNally F, Vale R (1993) Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell 75:419–429

    Article  CAS  Google Scholar 

  2. Hartman J, Vale RD (1999) Microtubule disassembly by ATP-dependent oligomerization of the AAA enzyme katanin. Science 286:782–785

    Article  CAS  Google Scholar 

  3. Quarmby L (2000) Cellular Samurai: katanin and the severing of microtubules. J Cell Sci 113:2821–2827

    CAS  PubMed  Google Scholar 

  4. McNally KP, Bazirgan OA, McNally FJ (2000) Two domains of p80 katanin regulate microtubule severing and spindle pole targeting by p60 katanin. J Cell Sci 113:1623–1633

    CAS  PubMed  Google Scholar 

  5. Buster D, McNally K, McNally FJ (2002) Katanin inhibition prevents the redistribution of gamma-tubulin at mitosis. J Cell Sci 115:1083–1092

    CAS  PubMed  Google Scholar 

  6. McNally K, Audhya A, Oegema K, McNally FJ (2006) Katanin controls mitotic and meiotic spindle length. J Cell Biol 175:881–891

    Article  CAS  Google Scholar 

  7. Poulain FE, Sobel A (2010) The microtubule net­work and neuronal morphogenesis: dynamic and coordinated orchestration through multi­ple players. Mol Cell Neurosci 43:15–32

    Article  CAS  Google Scholar 

  8. Baas PW, Qiang L (2005) Neuronal microtubules: when the MAP is the roadblock. Trends Cell Biol 15:183–187

    Article  CAS  Google Scholar 

  9. Baas PW, Vidya Nadar C, Myers KA (2006) Axonal transport of microtubules: the long and short of it. Traffic 7:490–498

    Article  CAS  Google Scholar 

  10. Yu W, Qiang L, Solowska JM, Karabay A, Korulu S, Baas PW (2008) The microtubule-severing pro­teins spastin and katanin participate differ­ently in the formation of axonal branches. Mol Biol Cell 19:1485–1498

    Article  CAS  Google Scholar 

  11. Hudson CD, Morris PJ, Latchman DS, Budhram-Mahadeo VS (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. J Biol Chem 280:11851–11858

    Article  CAS  Google Scholar 

  12. Ferreira A, Kosik KS (1996) Accelerated neuronal differentiation induced by p53 suppression. J Cell Sci 109:1509–1516

    CAS  PubMed  Google Scholar 

  13. Kim J, Lengner CJ, Kirak O, Hanna J, Cassady JP, Lodato MA, Wu S, Faddah DA, Steine EJ, 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

    Article  CAS  Google Scholar 

  14. Di Giovanni S, Knights CD, Rao M, Yakovlev A, Beers J, Catania J, Avantaggiati ML, Faden AI (2006) The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J 25:4084–4096

    Article  Google Scholar 

  15. Korulu S, Yildiz-Unal A, Yuksel M, Karabay A (2013) Protein kinase C activation causes neurite retraction via cyclinD1 and p60-katanin increase in rat hippocampal neurons. Eur J Neurosci 37(10):1610–1619

    Article  Google Scholar 

  16. Hartman JJ, Mahr J, McNally K, Okawa K, Iwamatsu A (1998) Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit. Cell 93:277–287

    Article  CAS  Google Scholar 

  17. Hansson LO, Friedler A, Freund S, Rudiger S, Fersht AR (2002) Two sequence motifs from HIF-1α bind to the DNA-binding site of p53. Proc Natl Acad Sci USA 99:10305–10309

    Article  CAS  Google Scholar 

  18. Sanchez-Puig N, Veprintsev DB, Fersht AR (2005) Binding of natively unfolded HIF-1α ODD domain to p53. Mol Cell 17:11–21

    Article  CAS  Google Scholar 

  19. Rudiger S, Freund SM, Veprintsev DB, Fersht AR (2002) CRINEPT-TROSY NMR reveals p53 core domain bound in an unfolded form to the chaperone Hsp90. Proc Natl Acad Sci USA 99:11085–11090

    Article  CAS  Google Scholar 

  20. Buchhop S, Gibson MK, Wang XW, Wagner P, Sturzbecher HW, Harris CC (1997) Interaction of p53 with the human Rad51 protein. Nucleic Acids Res 25:3868–3874

    Article  CAS  Google Scholar 

  21. Friedler A, Veprintsev DB, Rutherford T, von Glos KI, Fersht AR (2005) Binding of Rad51 and other peptide sequences to a promiscuous, highly electrostatic binding site in p53. J Biol Chem 280:8051–8059

    Article  CAS  Google Scholar 

  22. Petros AM, Gunasekera A, Xu N, Olejniczak ET, Fesik SW (2004) Defining the p53 DNA-binding domain/Bcl-x(L)-binding interface using NMR. FEBS Lett 559:171–174

    Article  CAS  Google Scholar 

  23. Sot B, Freund SM, Fersht AR (2007) Comparative biophysical characterization of p53 with the pro-apoptotic BAK and the anti-apoptotic BCL-xL. J Biol Chem 282:29193–29200

    Article  CAS  Google Scholar 

  24. ATCC (2013) p53 Hotspot mutation cell panels. https://www.atcc.org/en/Documents/Learning_Center/~/media/5F7B1CCACF724E3398BE56BFBEE3EFE4.ashx. Accessed 3 Oct 2019

Download references

Acknowledgements

We are grateful to Kübra Yener for helping in cloning the deletion constructs and Koray Kırımtay for his help in preliminary Co-IP studies.

Funding

This work was supported by the Scientific and Technological Research Council of Turkey (Grant No. 114Z971 to SK).

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Science and Letters, Istanbul Arel University, 34537, Istanbul, Turkey

    Sirin Korulu

  2. Institute of Natural and Health Sciences, Tallinn University, 10120, Tallinn, Estonia

    Sirin Korulu

  3. Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Mugla, 48000, Turkey

    Aysegul Yildiz

Authors
  1. Sirin Korulu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aysegul Yildiz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SK conceived the study, designed and carried out experiments, and contributed to writing the manuscript. AY contributed to writing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sirin Korulu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. S1 (PDF 213 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Korulu, S., Yildiz, A. p60-katanin: a novel interacting partner for p53. Mol Biol Rep 47, 4295–4301 (2020). https://doi.org/10.1007/s11033-020-05557-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05557-6

Keywords

Search

Navigation