Evidence for participation of a calpain-like cysteine protease in cell cycle progression through late G1 phase.
Recent studies have demonstrated that cell-permeant protease inhibitors arrest human fibroblasts in late G1. The target for the inhibitors has been claimed to be either the proteasome, or a calpain-like cysteine protease activity. In the present investigation, the progression of serum-stimulated WI-38 fibroblasts into S-phase was partially inhibited by the cell-permeant general inhibitor of cysteine proteases, E64d, but not by its non-permeant anolog, E64c. Exposure of fibroblasts in late G1 to the proteasome inhibitor, lactacystin, produced only a modest inhibition of progression into S-phase, and did not influence the extensive inhibition produced by the calpain-selective inhibitor, ZLLY-DMK. ZLLnV-CHO and ZLLL-CHO, which are reportedly selective for the proteasome, were less potent than ZLLY-DMK as inhibitors of S-phase progression. These results argue for the involvement of a calpain-like protease acting in late G1 to allow transit into S-phase.
Mellgren
R L
RL
Department of Pharmacology and Therapeutics, Medical College of Ohio, Toledo 43699-0008, USA.
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D003978:Diazomethane / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009842:Oligopeptides; C090218:benzyloxycarbonylleucyl-leucyl-tyrosine diazomethyl ketone; C067713:lactacystin; D003978:Diazomethane; D002154:Calpain; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine