1. Academic Validation
  2. Cytosolic carboxypeptidase 1 is involved in processing α- and β-tubulin

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

  • J Biol Chem. 2012 Feb 24;287(9):6503-17. doi: 10.1074/jbc.M111.309138.
Iryna Berezniuk 1 Hang T Vu Peter J Lyons Juan J Sironi Hui Xiao Berta Burd Mitsutoshi Setou Ruth H Angeletti Koji Ikegami Lloyd D Fricker
Affiliations

Affiliation

  • 1 Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
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.

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