26S proteasome regulation of Ankrd1/CARP in adult rat ventricular myocytes and human microvascular endothelial cells.
Ankyrin repeat domain 1 protein (Ankrd1), also known as cardiac ankyrin repeat protein (CARP), increases dramatically after tissue injury, and its overexpression improves aspects of wound healing. Reports that Ankrd1/CARP protein stability may affect cardiovascular organization, together with our findings that the protein is crucial to stability of the cardiomyocyte sarcomere and increased in wound healing, led us to compare the contribution of Ankrd1/CARP stability to its abundance. We found that the 26S proteasome is the dominant regulator of Ankrd1/CARP degradation, and that Ankrd1/CARP half-life is significantly longer in cardiomyocytes (h) than endothelial cells (min). In addition, higher endothelial cell density decreased the abundance of the protein without affecting steady state mRNA levels. Taken together, our data and that of others indicate that Ankrd1/CARP is highly regulated at multiple levels of its expression. The striking difference in protein half-life between a muscle and a non-muscle cell type suggests that post-translational proteolysis is correlated with the predominantly structural versus regulatory role of the protein in the two cell types.
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2561, USA.
Susan E
SE
Samaras
Billy
B
Chen
Stephen R
SR
Koch
Douglas B
DB
Sawyer
Chee Chew
CC
Lim
Jeffrey M
JM
Davidson
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006207:Half-Life; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D055806:Microvessels / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*
C491304:ANKRD1 protein, human; C491303:Ankrd1 protein, rat; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease