title: The cytosolic carboxypeptidases CCP2 and CCP3 catalyze posttranslational removal of acidic amino acids.
abstract: The posttranslational modification of carboxy-terminal tails of tubulin plays an important role in the regulation of the microtubule cytoskeleton. Enzymes responsible for deglutamylating tubulin have been discovered within a novel family of mammalian cytosolic carboxypeptidases. The discovery of these enzymes also revealed the existence of a range of other substrates that are enzymatically deglutamylated. Only four of six mammalian cytosolic carboxypeptidases had been enzymatically characterized. Here we complete the functional characterization of this protein family by demonstrating that CCP2 and CCP3 are deglutamylases, with CCP3 being able to hydrolyze aspartic acids with similar efficiency. Deaspartylation is a novel posttranslational modification that could, in conjunction with deglutamylation, broaden the range of potential substrates that undergo carboxy-terminal processing. In addition, we show that CCP2 and CCP3 are highly regulated proteins confined to ciliated tissues. The characterization of two novel enzymes for carboxy-terminal protein modification provides novel insights into the broadness of this barely studied process.
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona), Spain Institut Curie, 91405 Orsay, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Tort
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona), Spain Department of Medical Protein Research, VIB, 9000 Ghent, Belgium Department of Biochemistry, Ghent University, 9000 Ghent, Belgium.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Tanco
authors.affiliation: Institut Curie, 91405 Orsay, France PSL Research University, 75005 Paris, France Centre National de la Recherche Scientifique, UMR3306, 91405 Orsay, France Institut National de la Santé et de la Recherche Médicale, U1005, 91405 Orsay, France.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rocha
authors.affiliation: PSL Research University, 75005 Paris, France Department of Genetics, Institut Curie, 75248 Paris, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.affiliation: Centro de Estudos de Doenças Crónicas, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Seixas
authors.affiliation: Institut des Neurosciences de Grenoble, Institut National de la Santé et de la Recherche Médicale, U836, CEA, Université Joseph Fourier, 38042 Grenoble, France Université Grenoble Alpes, 38000 Grenoble, France CEA, Institut de Recherches en Technologies et Sciences pour le Vivant, 38000 Grenoble, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bosc
authors.affiliation: Institut des Neurosciences de Grenoble, Institut National de la Santé et de la Recherche Médicale, U836, CEA, Université Joseph Fourier, 38042 Grenoble, France Université Grenoble Alpes, 38000 Grenoble, France CEA, Institut de Recherches en Technologies et Sciences pour le Vivant, 38000 Grenoble, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
authors.affiliation: Institut des Neurosciences de Grenoble, Institut National de la Santé et de la Recherche Médicale, U836, CEA, Université Joseph Fourier, 38042 Grenoble, France Université Grenoble Alpes, 38000 Grenoble, France CEA, Institut de Recherches en Technologies et Sciences pour le Vivant, 38000 Grenoble, France.
authors.forename: Marie-Jo
authors.initials: MJ
authors.lastname: Moutin
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona), Spain.
authors.forename: Francesc Xavier
authors.initials: FX
authors.lastname: Avilés
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona), Spain Julia.Lorenzo@uab.cat Carsten.Janke@curie.fr.
authors.forename: Julia
authors.initials: J
authors.lastname: Lorenzo
authors.affiliation: Institut Curie, 91405 Orsay, France PSL Research University, 75005 Paris, France Centre National de la Recherche Scientifique, UMR3306, 91405 Orsay, France Institut National de la Santé et de la Recherche Médicale, U1005, 91405 Orsay, France Julia.Lorenzo@uab.cat Carsten.Janke@curie.fr.
authors.forename: Carsten
authors.initials: C
authors.lastname: Janke
mesh_terms: D008841:Actin Cytoskeleton; D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002268:Carboxypeptidases / Q000378:metabolism; D020134:Catalytic Domain; D002460:Cell Line; D002923:Cilia / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D053804:Granzymes / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; D002268:Carboxypeptidases; D053804:Granzymes; C509216:Gzmc protein, mouse; C056484:Gzme protein, mouse
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