PUBLICATION
Tumor suppressor RARRES1 interacts with cytoplasmic carboxypeptidase AGBL2 to regulate the α-tubulin tyrosination cycle
- Authors
- Sahab, Z.J., Hall, M.D., Me Sung, Y., Dakshanamurthy, S., Ji, Y., Kumar, D., Byers, S.W.
- ID
- ZDB-PUB-200212-22
- Date
- 2011
- Source
- Cancer research 71: 1219-28 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Carboxypeptidases/metabolism*
- Carboxypeptidases/physiology
- Cells, Cultured
- Cytoplasm/metabolism
- Humans
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Membrane Proteins/physiology
- Models, Molecular
- Molecular Sequence Data
- Phylogeny
- Protein Binding/genetics
- Protein Binding/physiology
- Protein Conformation
- Protein Processing, Post-Translational/genetics
- Sequence Homology, Amino Acid
- Tubulin/metabolism*
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/metabolism
- Tumor Suppressor Proteins/physiology
- Tyrosine/metabolism*
- PubMed
- 21303978 Full text @ Cancer Res.
Citation
Sahab, Z.J., Hall, M.D., Me Sung, Y., Dakshanamurthy, S., Ji, Y., Kumar, D., Byers, S.W. (2011) Tumor suppressor RARRES1 interacts with cytoplasmic carboxypeptidase AGBL2 to regulate the α-tubulin tyrosination cycle. Cancer research. 71:1219-28.
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 α-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 α-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping