In:
Genes to Cells, Wiley, Vol. 1, No. 7 ( 1996-07), p. 673-685
Abstract:
Background : The Nedd2/Ich‐1 protein belongs to a growing family of mammalian cysteine proteases similar to interleukin‐1β converting enzyme (ICE). Because of their similarity to the Caenorhabditis elegans cell death protein CED‐3, the ICE‐like proteins are thought to play a key role in the execution of apoptosis. The active form of ICE is a tetramer consisting of two heterodimers (p20 + p10) 2 derived from the cleavage of the pro‐enzyme. Results : In the present communication we show that the p51 Nedd2 precursor (pro‐Nedd2) is also cleaved into p20‐like (p19) and p10‐like (p12) subunits by extracts prepared from cultured cell lines. Extracts from apoptotic NIH‐3T3 cells but not normal growing NIH‐3T3 cells also contained pro‐Nedd2 cleaving activity. The processing of pro‐Nedd2 by cell extracts was inhibited by characteristic inhibitors of ICE‐like proteases. Additionally we show that pro‐Nedd2 (p51) can be processed in vitro by active CPP32 and ICE, and to a lesser extent by Mch2 and Nedd2. Granzyme B, a serine protease required for cytotoxic T lymphocyte (CTL) mediated killing of target cells, also cleaved pro‐Nedd2 to p19 + p12 subunits. Conclusions : Our observations suggest that Nedd2 activation requires cleavage by one or more ICE‐like proteases that lie upstream in the proteolytic cascade. Cleavage of pro‐Nedd2 by granzyme B indicates that Nedd2 may be one of the downstream effectors in the CTL‐mediated killing of target cells.
Type of Medium:
Online Resource
ISSN:
1356-9597
,
1365-2443
DOI:
10.1046/j.1365-2443.1996.00255.x
Language:
English
Publisher:
Wiley
Publication Date:
1996
detail.hit.zdb_id:
2020308-1
SSG:
12
Permalink