Skip to main content

Mathematical Modeling of Nuclear Trafficking of FOXO Transcription Factors

  • Protocol
  • First Online:
FOXO Transcription Factors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1890))

Abstract

Nuclear cytoplasmic flux of Foxo transcription factors is paramount in cellular gene regulation. For example, excluding Foxo from skeletal muscle nuclei is necessary to avoid muscle wasting through elevated protein breakdown. Constructing a mathematical model of the signaling process leading to alteration of Foxo nuclear cytoplasm ratio is useful in predicting and interpreting such ratio changes. In this chapter we derive a general mathematical model for nuclear cytoplasmic flux. We apply this model to Foxo flux and take advantage of rapid phosphorylation approximation and conservation conditions to reduce the Foxo flux model. We constrain our model with data from mouse skeletal muscle with applied IGF. This procedure provides an example of what might be called the central approach of mathematical modeling: The cycling of a biological question through mathematical formulation and back to biological interpretation.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Huang H, Tindall DJ (2007) Dynamic FoxO transcription factors. J Cell Sci 120(Pt 15):2479–2487

    Article  CAS  Google Scholar 

  2. Obsil T, Obsilova V (2008) Structure/function relationships underlying regulation of FOXO transcription factors. Oncogene 27:2263–2275

    Article  CAS  Google Scholar 

  3. Van Der Heide LP, Hoekman MF, Smidt MP (2004) The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation. Biochem J 380(Pt 2):297–309

    Article  Google Scholar 

  4. Zhao X, Gan L, Pan H, Kan D, Majeski M, Adam SA, Unterman TG (2004) Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms. Biochem J 378(Pt 3):839–849

    Article  CAS  Google Scholar 

  5. James K, Alfred S, Robert J (2009) Mathematical physiology I: cellular physiology. Springer-Verlag, New York

    Google Scholar 

  6. Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M, Yancopoulos GD, Glass DJ (2004) The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 14:395–403

    Article  CAS  Google Scholar 

  7. Calnan DR, Brunet A (2008) The FoxO code. Oncogene 27:2276–2288

    Article  CAS  Google Scholar 

  8. Schachter TN, Shen T, Liu Y, Schneider MF (2012) Kinetics of nuclear-cytoplasmic translocation of Foxo1 and Foxo3A in adult skeletal muscle fibers. Am J Physiol Cell Physiol 303:C977–C990

    Article  CAS  Google Scholar 

  9. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294(5547):1704–1708

    Article  CAS  Google Scholar 

  10. Wimmer RJ, Liu Y, Schachter TN, Stonko DP, Peercy BE, Schneider MF (2014) Mathematical modeling reveals modulation of both nuclear influx and efflux of Foxo1 by the IGF-I/PI3K/Akt pathway in skeletal muscle fibers. Am J Phys Cell Phys 306(6):C570–C584

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin F. Schneider .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Peercy, B.E., Schneider, M.F. (2019). Mathematical Modeling of Nuclear Trafficking of FOXO Transcription Factors. In: Link, W. (eds) FOXO Transcription Factors. Methods in Molecular Biology, vol 1890. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-8900-3_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8900-3_17

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-8899-0

  • Online ISBN: 978-1-4939-8900-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics