Calreticulin and Arginylated Calreticulin Have Different Susceptibilities to Proteasomal Degradation |
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Authors: | Victor E Goitea Marta E Hallak |
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Institution: | 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 |
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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. |
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Keywords: | post-translational modification (PTM) proteasome protein degradation protein turnover ubiquitylation (ubiquitination) arginylation calreticulin dimer |
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