Open AccessKIPase activity is a novel caspase‐like activity associated with cell proliferation
Author(s) -
MedinaPalazon Cahora,
Bernard Emmanuelle,
Frost Victoria,
Morley Simon,
Sinclair Alison J.
Publication year - 2004
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.2004.04200.x
Subject(s) - caspase , jurkat cells , apoptosis , biology , microbiology and biotechnology , cell culture , cell growth , programmed cell death , biochemistry , chemistry , t cell , immunology , genetics , immune system
A novel caspase‐like activity, which is directly regulated with cell proliferation is a candidate to regulate the abundance of the cyclin‐dependent kinase inhibitor, p27 KIP1 , in human lymphoid cells. This activity, which we term KIPase activity, can also cleave a subset of caspase substrates. Here we demonstrate that KIPase is a novel enzyme distinct from any of the previously characterized human caspases. We show that KIPase is active in a variety of cell lineages, its activity is associated with the proliferation of the human T‐cell line, Jurkat, and is not inhibited by the broad spectrum caspase inhibitor z‐VAD‐fmk. Gel filtration analysis revealed that KIPase has a native molecular mass of approximately 100–200 kDa. Furthermore, the activity of KIPase does not change during apoptosis induced by either ligation of FAS or exposure of cells to etoposide. The uniqueness of KIPase is demonstrated by the fact that none of the human caspases tested (1–10) are able to cleave a specific KIPase substrate (Ac‐DPSD‐AMC) and that an aldehyde modified derivative of the DPSD tetra peptide is unable to inhibit caspases, but is a good inhibitor of KIPase activity. This supports a hypothesis whereby KIPase is a currently unidentified caspase‐like enzyme which regulates the abundance of p27 KIP1 in a proliferation‐dependent manner.