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N-terminus cleavage of bcl-2 by a novel cellular non-ICE cysteine proteinase.
- Source :
- Leukemia (08876924); Sep98, Vol. 12 Issue 9, p1467-1472, 6p
- Publication Year :
- 1998
-
Abstract
- The bcl-2 protein plays an essential role in preventing cell death. Its activity is regulated through association with bcl-2 homologous and nonhomologous proteins and also by serine phosphorylation. We now report that bcl-2 can be proteolytically cleaved towards its N-terminus by a cysteine proteinase present in RL-7 lymphoma cell lysates, yielding a major product of apparent MW 20 kDa, different from the products of bcl-2 cleavage by HIV protease. Moreover, bcl-2 proteins mutated for Asp residues at positions 31 and 34 were efficiently cleaved by RL-7 cell lysates, indicating that this proteolytic activity is distinct from the caspase-3 that cleaves bcl-2 at Asp 34. This bcl-2 cleaving activity is inhibited by E-64 and is therefore distinct from the proteinases of the ICE/Ced-3 family (caspases), whereas reciprocally, ICE (caspase-1) is unable to cleave bcl-2. It is optimally active at pH 5, a feature distinguishing it from calpain, another non-ICE cysteine proteinase which has been associated with apoptosis. This novel bcl-2 cleaving protease, although constitutively present in RL-7 cells and resting peripheral blood lymphocytes (PBL) was upregulated following induction of apoptosis in RL-7 cells or mitogen activation in PBL. The N-terminus of bcl-2 which contains the BH4 domain that binds the kinase Raf-1 and the phosphatase calcineurin is essential for anti-apoptotic activity. Its cleavage might provide a novel post-translational mechanism for regulating bcl-2 function and could amplify ongoing programmed cell death. [ABSTRACT FROM AUTHOR]
- Subjects :
- PROTEINS
CELL death
CYSTEINE proteinases
APOPTOSIS
PROTEIN metabolism
B cell lymphoma
BIOCHEMISTRY
PHYSICAL & theoretical chemistry
COMPARATIVE studies
PHENOMENOLOGY
RESEARCH methodology
MEDICAL cooperation
PAPER chromatography
PEPTIDES
PROTEOLYTIC enzymes
RESEARCH
PROTEASE inhibitors
EVALUATION research
CANCER cell culture
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 12
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 8884074
- Full Text :
- https://doi.org/10.1038/sj.leu.2401132