MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis.

Abstract:

:MEK kinase 1 (MEKK1) is a 196-kDa protein that, in response to genotoxic agents, was found to undergo phosphorylation-dependent activation. The expression of kinase-inactive MEKK1 inhibited genotoxin-induced apoptosis. Following activation by genotoxins, MEKK1 was cleaved in a caspase-dependent manner into an active 91-kDa kinase fragment. Expression of MEKK1 stimulated DEVD-directed caspase activity and induced apoptosis. MEKK1 is itself a substrate for CPP32 (caspase-3). A mutant MEKK1 that is resistant to caspase cleavage was impaired in its ability to induce apoptosis. These findings demonstrate that MEKK1 contributes to the apoptotic response to genotoxins. The regulation of MEKK1 by genotoxins involves its activation, which may be part of survival pathways, followed by its cleavage, which generates a proapoptotic kinase fragment able to activate caspases. MEKK1 and caspases are predicted to be part of an amplification loop to increase caspase activity during apoptosis.

journal_name

Mol Cell Biol

authors

Widmann C,Gerwins P,Johnson NL,Jarpe MB,Johnson GL

doi

10.1128/mcb.18.4.2416

subject

Has Abstract

pub_date

1998-04-01 00:00:00

pages

2416-29

issue

4

eissn

0270-7306

issn

1098-5549

journal_volume

18

pub_type

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