title: Calreticulin and Arginylated Calreticulin Have Different Susceptibilities to Proteasomal Degradation.
abstract: Post-translational arginylation has been suggested to target proteins for proteasomal degradation. The degradation mechanism for arginylated calreticulin (R-CRT) localized in the cytoplasm is unknown. To evaluate the effect of arginylation on CRT stability, we examined the metabolic fates and degradation mechanisms of cytoplasmic CRT and R-CRT in NIH 3T3 and CHO cells. Both CRT isoforms were found to be proteasomal substrates, but the half-life of R-CRT (2 h) was longer than that of cytoplasmic CRT (0.7 h). Arginylation was not required for proteasomal degradation of CRT, although R-CRT displays ubiquitin modification. A CRT mutant incapable of dimerization showed reduced metabolic stability of R-CRT, indicating that R-CRT dimerization may protect it from proteasomal degradation. Our findings, taken together, demonstrate a novel function of arginylation: increasing the half-life of CRT in cytoplasm.
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo Nacional de Investigaciones Científicas y Técnicas, and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Goitea
authors.affiliation: From the Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Consejo Nacional de Investigaciones Científicas y Técnicas, and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina mhallak@fcq.unc.edu.ar.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Hallak
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D016466:CHO Cells; D037282:Calreticulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006207:Half-Life; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D037282:Calreticulin; D025801:Ubiquitin; D001120:Arginine; D046988:Proteasome Endopeptidase Complex
keywords: arginylation; calreticulin; dimer; post-translational modification (PTM); proteasome; protein degradation; protein turnover; ubiquitylation (ubiquitination)