Microtubule-dependent nuclear-cytoplasmic shuttling of Runx2

Shirwin M. Pockwinse, Arun Rajgopal, Daniel W. Young, Khwaja A. Mujeeb, Jeffrey Nickerson, Amjad Javed, Sambra Redick, Jane B. Lian, Andre J van Wijnen, Janet L. Stein, Gary S. Stein, Stephen J. Doxsey

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

RUNX/AML transcription factors are critical regulators of cell growth and differentiation in multiple lineages and have been linked to human cancers including acute myelogenous leukemia (RUNX1), as well as breast (RUNX2) and gastric cancers (RUNX3). RUNX proteins are targeted to gene regulatory micro-environments within the nucleus via a specific subnuclear targeting signal. However, the dynamics of RUNX distribution and compartmentalization between the cytoplasm and nucleus is minimally understood. Here we show by immunofluorescence microscopy that RUNX2 relocates from the nucleus to the cytoplasm when microtubules are stabilized by the chemotherapeutic agent taxol. The taxol-dependent cytoplasmic accumulation of RUNX2 is inhibited by leptomycin B, which blocks CRM-1 dependent nuclear export, and is not affected by the protein synthesis inhibitor cycloheximide. Using biochemical assays, we show that endogenous RUNX2 associates with stabilized microtubules in a concentration-dependent manner and that the RUNX2 amino terminus mediates the microtubule association. In soluble fractions of cells, RUNX2 co-immunoprecipitates α tubulin suggesting that microtubule binding involves the α/β tubulin subunits. We conclude that RUNX2 associates with microtubules and shuttles between the nucleus and the cytoplasm. We propose that nuclear-cytoplasmic shuttling of RUNX2 may modulate its transcriptional activity, as well as its ability to interface with signal transduction pathways that are integrated at RUNX2 containing subnuclear sites. It is possible that taxol-induced acute depletion of the nuclear levels of RUNX2 and/or other cell growth regulatory factors may represent an alternative pathway by which taxol exerts its biological effects during cancer chemotherapies.

Original languageEnglish (US)
Pages (from-to)354-362
Number of pages9
JournalJournal of Cellular Physiology
Volume206
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

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Paclitaxel
Microtubules
Cell growth
Tubulin
Cytoplasm
Signal transduction
Protein Synthesis Inhibitors
Chemotherapy
Cycloheximide
Cell Nucleus Active Transport
Assays
Regulator Genes
Microscopic examination
Transcription Factors
Fluorescence Microscopy
Acute Myeloid Leukemia
Genes
Association reactions
Stomach Neoplasms
Cell Differentiation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Pockwinse, S. M., Rajgopal, A., Young, D. W., Mujeeb, K. A., Nickerson, J., Javed, A., ... Doxsey, S. J. (2006). Microtubule-dependent nuclear-cytoplasmic shuttling of Runx2. Journal of Cellular Physiology, 206(2), 354-362. https://doi.org/10.1002/jcp.20469

Microtubule-dependent nuclear-cytoplasmic shuttling of Runx2. / Pockwinse, Shirwin M.; Rajgopal, Arun; Young, Daniel W.; Mujeeb, Khwaja A.; Nickerson, Jeffrey; Javed, Amjad; Redick, Sambra; Lian, Jane B.; van Wijnen, Andre J; Stein, Janet L.; Stein, Gary S.; Doxsey, Stephen J.

In: Journal of Cellular Physiology, Vol. 206, No. 2, 02.2006, p. 354-362.

Research output: Contribution to journalArticle

Pockwinse, SM, Rajgopal, A, Young, DW, Mujeeb, KA, Nickerson, J, Javed, A, Redick, S, Lian, JB, van Wijnen, AJ, Stein, JL, Stein, GS & Doxsey, SJ 2006, 'Microtubule-dependent nuclear-cytoplasmic shuttling of Runx2', Journal of Cellular Physiology, vol. 206, no. 2, pp. 354-362. https://doi.org/10.1002/jcp.20469
Pockwinse SM, Rajgopal A, Young DW, Mujeeb KA, Nickerson J, Javed A et al. Microtubule-dependent nuclear-cytoplasmic shuttling of Runx2. Journal of Cellular Physiology. 2006 Feb;206(2):354-362. https://doi.org/10.1002/jcp.20469
Pockwinse, Shirwin M. ; Rajgopal, Arun ; Young, Daniel W. ; Mujeeb, Khwaja A. ; Nickerson, Jeffrey ; Javed, Amjad ; Redick, Sambra ; Lian, Jane B. ; van Wijnen, Andre J ; Stein, Janet L. ; Stein, Gary S. ; Doxsey, Stephen J. / Microtubule-dependent nuclear-cytoplasmic shuttling of Runx2. In: Journal of Cellular Physiology. 2006 ; Vol. 206, No. 2. pp. 354-362.
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