A subset of caspase substrates functions as the Jekyll and Hyde of apoptosis

Détails

ID Serval
serval:BIB_27090F2FDA36
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
A subset of caspase substrates functions as the Jekyll and Hyde of apoptosis
Périodique
European Cytokine Network
Auteur(s)
Yang  J. Y., Widmann  C.
ISSN
1148-5493 (Print)
Statut éditorial
Publié
Date de publication
12/2002
Volume
13
Numéro
4
Pages
404-6
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Oct-Dec
Résumé
Cleavage of caspase substrates is believed to be the commitment point that will lead a cell towards apoptosis. While the cleavage of some caspase substrates participates directly in the dismantling of the cell, others regulate the extent of caspase activation. In this communication, we discuss some recent findings indicating that two caspase substrates, MEKK1 and RasGAP, change their functions from anti- to pro-apoptotic as caspase activity increases. MEKK1 is a MAPK kinase kinase regulating the JNK MAPK pathway. As a full-length protein, MEKK1 generates protective signals (e.g. in cardiomyocytes), but potentiates apoptosis when cleaved by caspases. This switch is mediated by a translocation of the kinase activity from insoluble to soluble cellular structures. RasGAP is a regulator of Ras GTPase family members. As a full-length protein, RasGAP does not modulate apoptosis. However, low caspase activity readily induces the cleavage of RasGAP into an N-terminal fragment that generates potent anti-apoptotic signals. At higher caspase activity, the N-terminal fragment is further cleaved into two fragments that strongly potentiate apoptosis. RasGAP can, thus, be viewed as an apoptostat because it allows the cells to determine when caspases have been mildly activated to fulfill functions other than apoptosis or when caspases are strongly activated to mediate apoptosis.
Mots-clé
Apoptosis/*physiology Caspases/*metabolism Humans *MAP Kinase Kinase Kinase 1 MAP Kinase Signaling System Protein-Serine-Threonine Kinases/physiology Substrate Specificity ras GTPase-Activating Proteins/physiology
Pubmed
Web of science
Création de la notice
24/01/2008 15:43
Dernière modification de la notice
20/08/2019 14:05
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