Cytosolic carboxypeptidase 1 is involved in processing α- and β-tubulin

Iryna Berezniuk, Hang T. Vu, Peter J. Lyons, Juan J. Sironi, Hui Xiao, Berta Burd, Mitsutoshi Setou, Ruth H. Angeletti, Koji Ikegami, Lloyd D. Fricker

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The Purkinje cell degeneration (pcd) mouse has a disruption in the gene encoding cytosolic carboxypeptidase 1 (CCP1). This study tested two proposed functions of CCP1: degradation of intracellular peptides and processing of tubulin. Overexpression (2-3-fold) or knockdown (80-90%) of CCP1 in human embryonic kidney 293T cells (HEK293T) did not affect the levels of most intracellular peptides but altered the levels of α-tubulin lacking two C-terminal amino acids (delta2-tubulin) ≥5-fold, suggesting that tubulin processing is the primary function of CCP1, not peptide degradation. Purified CCP1 produced delta2-tubulin from purified porcine brain α-tubulin or polymerized HEK293T microtubules. In addition, CCP1 removed Glu residues from the polyglutamyl side chains of porcine brain α- and β-tubulin and also generated a form of α-tubulin with two C-terminal Glu residues removed (delta3-tubulin). Consistent with this, pcd mouse brain showed hyperglutamylation of both α- and β-tubulin. The hyperglutamylation of α- and β-tubulin and subsequent death of Purkinje cells in pcd mice was counteracted by the knock-out of the gene encoding tubulin tyrosine ligase-like-1, indicating that this enzyme hyperglutamylates α- and β-tubulin. Taken together, these results demonstrate a role for CCP1 in the processing of Glu residues from β- as well as α-tubulin in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)6503-6517
Number of pages15
JournalJournal of Biological Chemistry
Volume287
Issue number9
DOIs
StatePublished - Feb 24 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Berezniuk, I., Vu, H. T., Lyons, P. J., Sironi, J. J., Xiao, H., Burd, B., Setou, M., Angeletti, R. H., Ikegami, K., & Fricker, L. D. (2012). Cytosolic carboxypeptidase 1 is involved in processing α- and β-tubulin. Journal of Biological Chemistry, 287(9), 6503-6517. https://doi.org/10.1074/jbc.M111.309138