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

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Updated: May 20, 2026

Detection of Protein Ubiquitination
09:00

Detection of Protein Ubiquitination

Published on: August 19, 2009

Svetlana V Kalinichenko1, Keiji Itoh, Elena V Korobko

  • 1Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.

Plos One
|June 30, 2012
PubMed

Insights

Researchers discovered Nedd4 regulates MAK-V protein kinase function, independent of its ubiquitin ligase activity. This finding sheds light on MAK-V

Area of Science:

  • Molecular biology
  • Cell signaling
  • Developmental biology

Background:

  • MAK-V/Hunk is an understudied AMPK-like protein kinase.
  • MAK-V plays roles in cell survival, apoptosis, embryonic development, and cancer.
  • The precise mechanisms of MAK-V regulation and function are largely unknown.

Purpose of the Study:

  • To identify regulators of MAK-V protein kinase activity.
  • To elucidate the molecular mechanisms underlying MAK-V function.

Main Methods:

  • Protein interaction studies to identify MAK-V binding partners.
  • Ubiquitin-proteasome system assays to assess MAK-V degradation.
  • Xenopus embryo development assays to evaluate functional rescue.

Main Results:

  • Nedd4, a HECT-type E3 ubiquitin ligase, was identified as a MAK-V interaction partner.
  • Nedd4 does not regulate MAK-V protein levels via the ubiquitin-proteasome system.
  • Nedd4 rescued MAK-V overexpression-induced developmental defects in Xenopus embryos in a ubiquitin ligase-independent manner.

Conclusions:

  • Nedd4 is the first identified regulator of MAK-V function.
  • The interaction between Nedd4 and MAK-V is physiologically relevant and impacts embryonic development.
  • Nedd4 regulates MAK-V activity through mechanisms distinct from its ubiquitin ligase function.

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