CALCIUM, PROTEASE ACTION, AND THE REGULATION OF THE CELL-CYCLE

Proteolysis is a key event in the control of the cell cycle. Most of t he proteins which are degraded at specific cycle points, e.g. cyclins A, B, and E, are substrates of the ubiquitin/proteasome pathway. The C a2+ dependent neutral protease calpain also cleaves cell cycle protein s, among them cyclin D1 and the c-mos proto-oncogene product which is a component of the CSF. The proteasome itself, however, may be under C a2+ control through the binding of Ca2+ to its 29 kDa regulatory subun it. Calpain undergoes relocation among cell compartments during the va rious steps of the mitotic and meiotic cycles. It promotes the initiat ion and the progression of mitosis when injected into the perinuclear space of synchronized PtK1, cells, and the resumption of meiosis when directly injected into the nuclei of prophase-arrested starfish oocyte s. Apart from the proteins mentioned above, most of the substrates of calpain which become cleaved during mitosis and meiosis are still unkn own. Microtubule-associated proteins are likely candidates.