Possible regulation of the skeletal muscle ryanodine receptor by a polyubiquitin binding subunit of the 26S proteasome.
Proteolytic digestion of ryanodine receptor (RyR) purified from skeletal muscle generated 25 short peptides. The amino acid sequences of two, 'KC5' and 'KC7', were absent from the RyR primary structure deduced by cDNA cloning. The sequence of KC7 corresponded to the N-terminus of the 12 kDa FK506-binding protein, which associates with the RyR and modulates its Ca2+ release channel (CRC) function. The sequence of KC5 was not similar to any proteins in the databases searched at that time. In the present study, the sequence of KC5 was compared to proteins in the current Swissprot database release and corresponds most closely to S5a, a proteasome subunit. Since S5a targets the 26S proteasome to polyubiquitinated proteins, and inositol 1,4,5-trisphosphate receptors, a related class of CRC, are down-regulated by a polyubiquitin-dependent mechanism in hormone stimulated cells, the abundance of RyRs may be controlled by association with this regulatory subunit.
Mackrill
J J
JJ
Department of Biochemistry, University College Cork, National University of Ireland, Cork, Ireland.
D000818:Animals; D001704:Biopolymers / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry; D019992:Databases as Topic; D015536:Down-Regulation / Q000502:physiology; D006360:Heat-Shock Proteins / Q000737:chemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018482:Muscle, Skeletal / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry; D010447:Peptide Hydrolases / Q000737:chemistry*; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D016415:Sequence Alignment; D022021:Tacrolimus Binding Proteins; D014452:Ubiquitins / Q000378:metabolism*
D001704:Biopolymers; D015220:Calcium Channels; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D014452:Ubiquitins; D025821:Polyubiquitin; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D022021:Tacrolimus Binding Proteins