Calreticulin and arginylated calreticulin follow different pathways of proteasomal degradation

the journal of biological chemistry

American Society for Biochemistry and Molecular Biology

Año: 2015 vol. 290 p. 16403 - 16403

ost-translational arginylation has been suggested to targetproteins for proteasomal degradation. The degradation mechanismfor arginylated calreticulin (R-CRT) localized in the cytoplasmis unknown. To evaluate the effect of arginylation onCRTstability, we examined the metabolic fates and degradationmechanisms of cytoplasmic CRT and R-CRT in NIH 3T3 andCHO cells. Both CRT isoforms were found to be proteasomalsubstrates, but the half-life of R-CRT (2 h) was longer than thatof cytoplasmic CRT (0.7 h). Arginylation was not required forproteasomal degradation of CRT, although R-CRT displaysubiquitin modification. A CRT mutant incapable of dimerizationshowed reduced metabolic stability of R-CRT, indicatingthat R-CRT dimerization may protect it from proteasomal degradation.Our findings, taken together, demonstrate a novelfunction of arginylation: increasing the half-life of CRT in cytoplasm.