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Tumor suppressor RARRES1 interacts with cytoplasmic carboxypeptidase AGBL2 to regulate the α-tubulin tyrosination

Ziad J Sahab1, Michael D Hall, You Me Sung

  • 1Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.

Cancer Research
|February 10, 2011
PubMed

Insights

Retinoic acid receptor responder 1 (RARRES1) loss in cancer cells reveals its function as a carboxypeptidase inhibitor. This finding uncovers a novel therapeutic target in the microtubule tyrosination cycle for cancer treatment.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Retinoic acid receptor responder 1 (RARRES1) is frequently methylated in cancers but its function remains unknown.
  • Loss of RARRES1 is observed in various cancer cells, especially those with a mesenchymal phenotype.

Purpose of the Study:

  • To elucidate the function of RARRES1 and its role in cancer.
  • To investigate the interaction between RARRES1 and ATP/GTP binding protein-like 2 (AGBL2).
  • To explore the implications of the RARRES1-AGBL2 interaction on microtubule dynamics and tumorigenesis.

Main Methods:

  • Investigated RARRES1's interaction with AGBL2, a cytoplasmic carboxypeptidase.
  • Utilized knockdown experiments for AGBL2 and RARRES1 to assess their effects on α-tubulin detyrosination.
  • Examined the involvement of RARRES1, AGBL2, Eg5/KIF11, and EB1 in the microtubule tyrosination cycle.

Main Results:

  • RARRES1 functions as a transmembrane carboxypeptidase inhibitor interacting with AGBL2.
  • AGBL2 knockdown impairs α-tubulin detyrosination, identifying it as a potential tubulin tyrosine carboxypeptidase.
  • RARRES1 knockdown enhances α-tubulin detyrosination, suggesting RARRES1 is an inhibitor of AGBL2.

Conclusions:

  • RARRES1 and AGBL2 are key regulators of the microtubule tyrosination cycle.
  • The RARRES1-AGBL2 axis and the microtubule tyrosination cycle are implicated in tumorigenesis.
  • This study identifies a new therapeutic avenue for cancer intervention targeting the microtubule tyrosination cycle.

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