Calcium- and proteasome-dependent degradation of the JNK scaffold protein islet-brain 1.
Details
Serval ID
serval:BIB_68939E882CF2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Calcium- and proteasome-dependent degradation of the JNK scaffold protein islet-brain 1.
Journal
Journal of Biological Chemistry
ISSN
0021-9258
Publication state
Published
Issued date
12/2003
Peer-reviewed
Oui
Volume
278
Number
49
Pages
48720-48726
Language
english
Notes
Publication types: Journal Article
Abstract
In models of type 1 diabetes, cytokines induce pancreatic beta-cell death by apoptosis. This process seems to be facilitated by a reduction in the amount of the islet-brain 1/JNK interacting protein 1 (IB1/JIP1), a JNK-scaffold with an anti-apoptotic effect. A point mutation S59N at the N terminus of the scaffold, which segregates in diabetic patients, has the functional consequence of sensitizing cells to apoptotic stimuli. Neither the mechanisms leading to IB1/JIP1 down-regulation by cytokines nor the mechanisms leading to the decreased capacity of the S59N mutation to protect cells from apoptosis are understood. Here, we show that IB1/JIP1 stability is modulated by intracellular calcium. The effect of calcium depends upon JNK activation, which primes the scaffold for ubiquitination-mediated degradation via the proteasome machinery. Furthermore, we observe that the S59N mutation decreases IB1/JIP1 stability by sensitizing IB1/JIP1 to calcium- and proteasome-dependent degradation. These data indicate that calcium influx initiated by cytokines mediates ubiquitination and degradation of IB1/JIP1 and may, therefore, provide a link between calcium influx and JNK-mediated apoptosis in pancreatic beta-cells.
Keywords
Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Base Sequence, Calcium/metabolism, Cell Line, Cysteine Endopeptidases/metabolism, DNA Primers, Down-Regulation, Humans, Hydrolysis, Islets of Langerhans/cytology, Islets of Langerhans/enzymology, Multienzyme Complexes/metabolism, Nuclear Proteins/genetics, Nuclear Proteins/metabolism, Point Mutation, Proteasome Endopeptidase Complex, Rats, Trans-Activators/genetics, Trans-Activators/metabolism, Ubiquitin/metabolism
Pubmed
Open Access
Yes
Create date
25/01/2008 17:18
Last modification date
20/08/2019 15:23