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

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...

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Bibliographic Details
Published in:PloS one 2012-06, Vol.7 (6), p.e39505
Main Authors: Kalinichenko, Svetlana V, Itoh, Keiji, Korobko, Elena V, Sokol, Sergei Y, Buchman, Vladimir L, Korobko, Igor V
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biology
Blotting, Western
Cancer metastasis
Cloning
Cycloheximide - pharmacology
Cytokines
Electrophoresis, Polyacrylamide Gel
Embryogenesis
Embryonic development
Embryonic growth stage
Embryos
Endosomal Sorting Complexes Required for Transport - genetics
Endosomal Sorting Complexes Required for Transport - metabolism
Experiments
Humans
Identification
Immunoglobulins
Insulin-like growth factors
Kinases
Ligases
MAK-V protein
Metastases
Mice
Molecular modelling
Nedd4 Ubiquitin Protein Ligases
PC12 Cells
Phosphorylation
Physiological aspects
Proteasomes
Protein Binding
Protein kinase
Protein kinases
Protein Kinases - genetics
Protein Kinases - metabolism
Proteins
Rats
Scientific imaging
Tumorigenesis
Ubiquitin
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitination - drug effects
V protein
Xenopus Proteins
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0039505