Differential arginylation of actin isoforms is regulated by coding sequence-dependent degradation.
The mammalian cytoskeletal proteins β- and γ-actin are highly homologous, but only β-actin is amino-terminally arginylated in vivo, which regulates its function. We examined the metabolic fate of exogenously expressed arginylated and nonarginylated actin isoforms. Arginylated γ-actin, unlike β-, was highly unstable and was selectively ubiquitinated and degraded in vivo. This instability was regulated by the differences in the nucleotide coding sequence between the two actin isoforms, which conferred different translation rates. γ-actin was translated more slowly than β-actin, and this slower processing resulted in the exposure of a normally hidden lysine residue for ubiquitination, leading to the preferential degradation of γ-actin upon arginylation. This degradation mechanism, coupled to nucleotide coding sequence, may regulate protein arginylation in vivo.
Zhang
Fangliang
F
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Saha
Sougata
S
Shabalina
Svetlana A
SA
Kashina
Anna
A
D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003062:Codon; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009690:Nucleic Acid Conformation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D046188:Protein Modification, Translational; D055550:Protein Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D054875:Ubiquitination
D000199:Actins; D003062:Codon; D020033:Protein Isoforms; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D001120:Arginine; D046988:Proteasome Endopeptidase Complex; D008239:Lysine