Abstract
NORE1A is a Ras-binding protein that belongs to a group of tumor suppressors known as the Ras association domain family. Their growth- and tumor-suppressive function is assumed to be dependent on association with the microtubule cytoskeleton. However, a detailed understanding of this interplay is still missing. Here, we show that NORE1A directly interacts with tubulin and is capable of nucleating microtubules. Strikingly, the ability to stimulate nucleation is regulated in a dual specific way either via phosphorylation of NORE1A within the Ras-binding domain by Aurora A kinase or via binding to activated Ras. We also demonstrate that NORE1A mediates a negative effect of activated Ras on microtubule nucleation. On the basis of our results, we propose a novel regulatory network composed of the tumor suppressor NORE1A, the mitotic kinase Aurora A, the small GTPase Ras, and the microtubule cytoskeleton.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Apoptosis Regulatory Proteins
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Aurora Kinase A
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Aurora Kinases
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Cell Line
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Humans
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Mice
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Microtubules / genetics
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Microtubules / metabolism*
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Monomeric GTP-Binding Proteins / genetics
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Monomeric GTP-Binding Proteins / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction / physiology*
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Tubulin / genetics
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Tubulin / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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ras Proteins / genetics
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ras Proteins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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RASSF5 protein, human
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Rassf5 protein, mouse
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Tubulin
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Tumor Suppressor Proteins
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Aurka protein, mouse
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Aurora Kinase A
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Aurora Kinases
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Protein Serine-Threonine Kinases
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Monomeric GTP-Binding Proteins
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ras Proteins