Cyclosporin A inhibits the degradation of signal sequences after processing of presecretory proteins by signal peptidase.
Targeting of presecretory proteins to, and insertion into, the microsomal membrane are mediated by signal sequences. These signal sequences are removed from presecretory proteins by signal peptidase. We demonstrate that the signal sequence of preprolactin, after translocation into microsomes and cleavage by signal peptidase, is converted to an intermediate form. This intermediate was found outside the microsomes, where it was degraded in the presence of cytosol. Degradation of the signal sequence of another presecretory protein, preprocecropinA, occurred even in the absence of cytosol. The immunosuppressant cyclosporin A inhibited trimming of the preprolactin signal sequence and degradation of the preprocecropinA signal sequence. We observed by cross-linking studies that cleaved signal sequences are bound to two microsomal proteins prior to degradation.
Klappa
P
P
Universität des Saarlandes, Homburg, Germany.
Dierks
T
T
Zimmermann
R
R
D000595:Amino Acid Sequence; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D007301:Insect Hormones / Q000737:chemistry / Q000378:metabolism*; D019476:Insect Proteins; D007700:Kinetics; D008081:Liposomes; D008565:Membrane Proteins; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism; D011388:Prolactin / Q000737:chemistry / Q000378:metabolism*; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021382:Protein Sorting Signals / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*
C059037:CecA2 protein, Bombyx mori; D007301:Insect Hormones; D019476:Insect Proteins; D008081:Liposomes; D008565:Membrane Proteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D011510:Proteolipids; D012333:RNA, Messenger; C020485:proteoliposomes; C017671:preprolactin; D016572:Cyclosporine; D011388:Prolactin; D012697:Serine Endopeptidases; C026515:type I signal peptidase