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Tumor suppressor RASSF1A is a microtubule-binding protein that stabilizes microtubules and induces G2/M arrest

Oncogene volume 23, pages 8216–8230 (2004)Cite this article

Abstract

RASSF1A is a putative tumor suppressor gene that is inactivated in a variety of human tumors. Expression of exogenous RASSF1A has been shown to inhibit tumor growth in vitro and in animals. However, the molecular mechanisms by which RASSF1A mediates its tumor suppressive effects remain to be elucidated. Here, we report that RASSF1A is a microtubule-binding protein that interacts with and stabilizes microtubules. We have identified the RASSF1A region harboring a basic domain that appears to mediate the interactions between RASSF1A and microtubules. The basic domain-containing RASSF1C isoform also interacts with and stabilizes microtubules. We further show that in addition to G1 arrest, RASSF1A promotes growth arrest in the G2/M phase of the cell cycle and endogenous RASSF1A also interacts with microtubules. Based on our results, we propose that RASSF1A may mediate its tumor suppressive effects by inducing growth arrest in the G1 and G2/M phases. Together, these results provide important new insights into the molecular mechanisms by which this novel tumor suppressor mediates its biological effects.

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Acknowledgements

We thank Dr Peter C Keng at the Cell Separation and Flow Cytometry Facility, University of Rochester for assisting in cell cycle analyses. This work was supported in part by National Institutes of Health Grants CA86945 and DK62136-01. Correspondence and requests for material should be addressed to YH.

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  1. Department of Pharmacology, State University of New York, Upstate Medical University, 750 E Adams Street, Syracuse, 13210, NY, USA

    Rong Rong, Weixin Jin, Jennifer Zhang, M Saeed Sheikh & Ying Huang

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  4. M Saeed Sheikh
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Correspondence to Ying Huang.

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Rong, R., Jin, W., Zhang, J. et al. Tumor suppressor RASSF1A is a microtubule-binding protein that stabilizes microtubules and induces G2/M arrest. Oncogene 23, 8216–8230 (2004). https://doi.org/10.1038/sj.onc.1207901

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