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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

TTC3 ubiquitination terminates Akt-ivation

Alex Toker1

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. atoker@bidmc.harvard.edu

Developmental Cell
|January 12, 2010
PubMed

Insights

A novel ubiquitination mechanism regulates Akt protein kinase activity. The E3 ubiquitin ligase TTC3 targets activated Akt for proteasomal degradation in the nucleus, impacting cell signaling pathways.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The Akt serine/threonine protein kinase is a crucial regulator of cell survival, proliferation, and metabolism.
  • Posttranslational modifications play a significant role in controlling protein activity and stability.
  • Understanding Akt regulation is vital for deciphering cellular processes and disease mechanisms.

Purpose of the Study:

  • To elucidate a novel mechanism for the posttranslational regulation of the Akt protein kinase.
  • To investigate the role of ubiquitination in Akt signaling.
  • To identify specific enzymes involved in modifying and regulating Akt.

Main Methods:

  • Utilized biochemical assays to study protein-protein interactions.
  • Employed ubiquitination assays to detect modification of Akt.
  • Investigated the subcellular localization of Akt and its regulators using cell imaging techniques.
  • Analyzed protein degradation using proteasome inhibition studies.

Main Results:

  • Identified TTC3 as an E3 ubiquitin ligase that interacts with Akt.
  • Demonstrated that TTC3 ubiquitinates phosphorylated and activated Akt.
  • Showed that ubiquitination by TTC3 targets Akt for proteasomal degradation.
  • Localized this regulatory process to the nucleus.

Conclusions:

  • Discovered a new pathway for Akt regulation through ubiquitination-mediated degradation.
  • TTC3 acts as a key regulator by targeting activated Akt for nuclear degradation.
  • This mechanism provides a novel layer of control over Akt signaling, impacting cellular functions.

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