| First Author | Berezniuk I | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 9 | Pages | 6503-17 |
| PubMed ID | 22170066 | Mgi Jnum | J:313952 |
| Mgi Id | MGI:6810285 | Doi | 10.1074/jbc.M111.309138 |
| Citation | Berezniuk I, et al. (2012) Cytosolic carboxypeptidase 1 is involved in processing alpha- and beta-tubulin. J Biol Chem 287(9):6503-17 |
| abstractText | 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 alpha-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 alpha-tubulin or polymerized HEK293T microtubules. In addition, CCP1 removed Glu residues from the polyglutamyl side chains of porcine brain alpha- and beta-tubulin and also generated a form of alpha-tubulin with two C-terminal Glu residues removed (delta3-tubulin). Consistent with this, pcd mouse brain showed hyperglutamylation of both alpha- and beta-tubulin. The hyperglutamylation of alpha- and beta-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 alpha- and beta-tubulin. Taken together, these results demonstrate a role for CCP1 in the processing of Glu residues from beta- as well as alpha-tubulin in vitro and in vivo. |
