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

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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.