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EMBO Rep. 2006 Nov;7(11):1147-53. Epub 2006 Oct 6.

Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains.

Author information

1
Unité de Signalisation Moléculaire et Activation Cellulaire, URA 2582, CNRS, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France.

Abstract

Deltex (DTX) and AIP4 are the human orthologues of the Drosophila deltex and Suppressor of deltex, which have been genetically described as being antagonistically involved in the Notch signalling pathway. Both genes encode E3 ubiquitin ligases of the RING (Really interesting new gene)-H2 and HECT (Homologous to E6AP carboxyl terminus) families, respectively. In an attempt to understand the molecular basis of their genetic interactions, we studied the relationship between DTX and AIP4 in the absence of activation of the Notch pathway. We show here that both molecules interact and partially colocalize to endocytic vesicles, and that AIP4 targets DTX for lysosomal degradation. Furthermore, AIP4-generated polyubiquitin chains are mainly conjugated through lysine 29 of ubiquitin in vivo, indicating a link between this type of chain and lysosomal degradation.

PMID:
17028573
PMCID:
PMC1679774
DOI:
10.1038/sj.embor.7400822
[Indexed for MEDLINE]
Free PMC Article

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