title: 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: Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
authors: Svetlana V
authors: SV
authors: Kalinichenko
authors: Keiji
authors: K
authors: Itoh
authors: Elena V
authors: EV
authors: Korobko
authors: Sergei Y
authors: SY
authors: Sokol
authors: Vladimir L
authors: VL
authors: Buchman
authors: Igor V
authors: IV
authors: Korobko
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003513:Cycloheximide / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D000075702:Nedd4 Ubiquitin Protein Ligases; D016716:PC12 Cells; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects; D029867:Xenopus Proteins
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D029867:Xenopus Proteins; D003513:Cycloheximide; C000618479:NEDD4L protein, rat; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618482:Nedd4 protein, Xenopus; C000618483:Nedd4 protein, human; C000618484:Nedd4 protein, rat; C000618461:Nedd4l protein, mouse; C000618460:nedd4l protein, Xenopus; D044767:Ubiquitin-Protein Ligases; C556300:HUNK protein, rat; D011494:Protein Kinases