The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation.
AuthorsZhang P, Wang C, Gao K, Wang D, Mao J, An J, Xu C, Wu D, Yu H, Liu JO, Yu L
JournalJ Biol Chem
PubMed ID20068034
'Thioredoxin interacting protein (TXNIP) was originally characterized as an endogenous inhibitor of thioredoxin, a key regulator in cellular redox homeostasis. TXNIP is also known to play important roles in tumor growth and metastasis, glucose and lipid metabolism. TXNIP expression is induced by various stress stimuli. However, it has been unclear ... More
Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets and interacts with the ubiquitin E3 ligases AIP4 and AIP5.
AuthorsEdwards TL, Clowes VE, Tsang HT, Connell JW, Sanderson CM, Luzio JP, Reid E
JournalBiochem J
PubMed ID19580544
'The HSPs (hereditary spastic paraplegias) are genetic conditions in which there is distal degeneration of the longest axons of the corticospinal tract, resulting in spastic paralysis of the legs. The gene encoding spartin is mutated in Troyer syndrome, an HSP in which paralysis is accompanied by additional clinical features. There ... More
The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid.
AuthorsAzakir BA, Desrochers G, Angers A
JournalFEBS J
PubMed ID20392206
'The truncated C-terminal portion of Bid (tBid) is an important intermediate in ligand-induced apoptosis. tBid has been shown to be sensitive to proteasomal inhibitors and downregulated by activation of the epidermal growth factor (EGF) pathway. Here, we provide evidence that tBid is a substrate of the ubiquitin ligase Itch, which ... More
The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4.
Ubiquitination of the chemokine receptor CXCR4 serves as a targeting signal for lysosomal degradation, but the mechanisms mediating ubiquitination and lysosomal sorting remain poorly understood. Here we report that the Nedd4-like E3 ubiquitin ligase AIP4 mediates ubiquitination of CXCR4 at the plasma membrane, and of the ubiquitin binding protein Hrs ... More
AuthorsWang Y, Du D, Fang L, Yang G, Zhang C, Zeng R, Ullrich A, Lottspeich F, Chen Z
JournalEMBO J
PubMed ID17053785
The conserved polarity complex, comprising the partitioning-defective (Par) proteins Par3 and Par6, and the atypical protein kinase C, functions in various cell-polarization events and asymmetric cell divisions. However, little is known about whether and how external stimuli-induced signals may regulate Par3 function in epithelial cell polarity. Here, we found that ... More
The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction.
AuthorsBhandari D, Robia SL, Marchese A
JournalMol Biol Cell
PubMed ID19116316
The E3 ubiquitin ligase atrophin interacting protein 4 (AIP4) mediates ubiquitination and down-regulation of the chemokine receptor CXCR4. AIP4 belongs to the Nedd4-like homologous to E6-AP carboxy terminus domain family of E3 ubiquitin ligases, which typically bind proline-rich motifs within target proteins via the WW domains. The intracellular domains of ... More