Tumor suppressor RARRES1 interacts with cytoplasmic carboxypeptidase AGBL2 to regulate the alpha-tubulin tyrosination cycle.
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Sahab ZJ, Hall MD, Me Sung Y, Dakshanamurthy S, Ji Y, Kumar D, Byers SW
Tumor suppressor RARRES1 interacts with cytoplasmic carboxypeptidase AGBL2 to regulate the alpha-tubulin tyrosination cycle.
Cancer Res. 2011 Feb 15;71(4):1219-28. doi: 10.1158/0008-5472.CAN-10-2294. Epub 2011 Feb 8.
- PubMed ID
- 21303978 [ View in PubMed]
- Abstract
Even though it is among the most commonly methylated loci in multiple cancers, the retinoic acid-induced tumor suppressor retinoic acid receptor responder 1 (RARRES1) has no known function. We now show that RARRES1 is lost in many cancer cells, particularly those with a mesenchymal phenotype, and is a transmembrane carboxypeptidase inhibitor that interacts with ATP/GTP binding protein-like 2 (AGBL2), a cytoplasmic carboxypeptidase. Knockdown of AGBL2 results in a failure of the cell to detyrosinate the C-terminal EEY region of alpha-tubulin and indicates that it is a candidate for the long sought-after tubulin tyrosine carboxypeptidase important in the regulation of microtubule dynamics. In contrast, knockdown of RARRES1 increases the level of detyrosinated alpha-tubulin consistent with a role as the cognate inhibitor of AGBL2. We conclude that RARRES1, its interacting partners AGBL2, Eg5/KIF11, another EEY-bearing protein (EB1), and the microtubule tyrosination cycle are important in tumorigenesis and identify a novel area for therapeutic intervention.