Identification of Nedd4 E3 ubiquitin ligase as a binding partner and regulator of MAK-V protein kinase.

Abstract	MAK-V/Hunk is a scantily characterized AMPK-like protein kinase. Recent findings identified MAK-V as a pro-survival and anti-apoptotic protein and revealed its role in embryonic development as well as in tumorigenesis and metastasis. However molecular mechanisms of MAK-V action and regulation of its activity remain largely unknown. We identified Nedd4 as an interaction partner for MAK-V protein kinase. However, this HECT-type E3 ubiquitin ligase is not involved in the control of MAK-V degradation by the ubiquitin-proteasome system that regulates MAK-V abundance in cells. However, Nedd4 in an ubiquitin ligase-independent manner rescued developmental defects in Xenopus embryos induced by MAK-V overexpression, suggesting physiological relevance of interaction between MAK-V and Nedd4. This identifies Nedd4 as the first known regulator of MAK-V function.
Authors	Svetlana V Kalinichenko, Keiji Itoh, Elena V Korobko, Sergei Y Sokol, Vladimir L Buchman, Igor V Korobko
Journal	PloS one (PLoS One) Vol. 7 Issue 6 Pg. e39505 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID	22745772 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Endosomal Sorting Complexes Required for Transport Xenopus Proteins Cycloheximide NEDD4L protein, rat Nedd4 Ubiquitin Protein Ligases Nedd4 protein, Xenopus Nedd4 protein, human Nedd4 protein, rat Nedd4l protein, mouse nedd4l protein, Xenopus Ubiquitin-Protein Ligases HUNK protein, rat Protein Kinases
Topics	Animals Blotting, Western Cycloheximide (pharmacology) Electrophoresis, Polyacrylamide Gel Endosomal Sorting Complexes Required for Transport (genetics, metabolism) Humans Mice Nedd4 Ubiquitin Protein Ligases PC12 Cells Protein Binding Protein Kinases (genetics, metabolism) Rats Ubiquitin-Protein Ligases (genetics, metabolism) Ubiquitination (drug effects) Xenopus Proteins

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