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Type: Journal article
Title: Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis
Author: Harvey, K.
Harvey, N.
Michael, J.
Parasivam, G.
Waterhouse, N.
Alnemri, E.
Watters, D.
Kumar, S.
Citation: Journal of Biological Chemistry, 1998; 273(22):13524-13530
Publisher: American Society for Biochemistry and Molecular Biology
Issue Date: 1998
ISSN: 1083-351X
Statement of
Kieran F. Harvey, Natasha L. Harvey, Julie M. Michael, Gayathri Parasivam, Nigel Waterhouse, Emad S. Alnemr, Dianne Watters and Sharad Kumar
Abstract: The onset of apoptosis is coupled to the proteolytic activation of a family of cysteine proteases, termed caspases. These proteases cleave their target proteins after an aspartate residue. Following caspase activation during apoptosis, a number of specific proteins have been shown to be cleaved. Here we show that Nedd4, a ubiquitin-protein ligase containing multiple WW domains and a calcium/lipid-binding domain, is also cleaved during apoptosis induced by a variety of stimuli including Fas-ligation, γ-radiation, tumor necrosis factor-α, C-8 ceramide, and etoposide treatment. Extracts from apoptotic cells also generated cleavage patterns similar to that seen in vivo, and this cleavage was inhibited by an inhibitor of caspase-3-like proteases. In vitro, Nedd4 was cleaved by a number of caspases, including caspase-1, -3, -6, and -7. By site-directed mutagenesis, one of the in vitro caspase cleavage sites in mouse Nedd4 was mapped to a DQPD²³⁷↓ sequence, which is conserved between mouse, rat, and human proteins. This is the first report demonstrating that an enzyme of the ubiquitin pathway is cleaved by caspases during apoptosis.
Keywords: Cell Line
Tumor Cells, Cultured
Cysteine Endopeptidases
Ubiquitin-Protein Ligases
Calcium-Binding Proteins
Peptide Mapping
Endosomal Sorting Complexes Required for Transport
Nedd4 Ubiquitin Protein Ligases
fas Receptor
Rights: © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI: 10.1074/jbc.273.22.13524
Appears in Collections:Aurora harvest 4
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