Related Experiment Video

Updated: Feb 8, 2026

The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells
09:34

The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells

Published on: July 27, 2018

18.7K

Cullin-3 adaptor SHKBP1 inhibits SQSTM1/p62 oligomerization and Keap1 sequestration

Lin Luan1,2, Xiaofu Cao1,3, Zijun Xia1,3

  • 1Weill Institute for Cell and Molecular Biology, Cornell University , Ithaca, NY, USA.

The Journal of Cell Biology
|February 6, 2026
PubMed

Insights

SHKBP1 regulates p62 body formation, impacting the antioxidant response independently of ubiquitination. This discovery reveals a new mechanism controlling cellular stress responses via protein interactions.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • SQSTM1/p62 is crucial for protein degradation via autophagy and ubiquitination, and regulates antioxidant responses.
  • p62 forms cytoplasmic p62 bodies, which are phase-separated structures essential for its functions.
  • Mechanisms controlling p62 body formation and dynamics are not fully understood.

Purpose of the Study:

  • To identify novel regulatory mechanisms of p62 oligomerization and p62 body formation.
  • To investigate the role of SHKBP1, a cullin-3 E3 ubiquitin ligase adaptor, in p62 regulation.
  • To elucidate the impact of SHKBP1-mediated p62 regulation on cellular antioxidant responses.

Main Methods:

  • Protein-protein interaction mapping between SHKBP1 and p62.
  • Analysis of p62 body formation and dynamics in the presence of SHKBP1.
  • Assessment of cellular antioxidant response pathways, including Keap1 sequestration and Nrf2 nuclear translocation.

Main Results:

  • SHKBP1 directly interacts with p62 outside of p62 bodies.
  • This interaction inhibits p62 oligomerization and limits its incorporation into p62 bodies.
  • SHKBP1-mediated regulation of p62 bodies affects the antioxidant response by influencing Keap1 sequestration and Nrf2 activation.

Conclusions:

  • SHKBP1 regulates p62 body formation through a non-ubiquitination-dependent mechanism.
  • This pathway provides a novel link between E3 ligase adaptors and the regulation of cellular oxidative stress responses.
  • The findings uncover a new layer of control over p62-mediated cellular signaling.

More Related Videos

In vivo and in vitro Studies of Adaptor-clathrin Interaction17:14

In vivo and in vitro Studies of Adaptor-clathrin Interaction

Published on: January 26, 2011

15.1K
Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry11:39

Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry

Published on: July 21, 2017

32.3K

Related Concept Videos

Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.2K
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
92.6K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.0K
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH301:11

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3

All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
7.5K
Piaget's Stage 3 of Cognitive Development01:17

Piaget's Stage 3 of Cognitive Development

During Piaget's concrete operational stage, from ages 7 to 11, children exhibit a marked increase in logical thinking skills, specifically in relation to tangible, real-world events. This stage is characterized by the development of several essential cognitive concepts, including conservation, reversibility, and classification, all of which support the child's evolving capacity for structured thought.
Conservation and Constancy of Quantity
A significant cognitive milestone in the...
1.1K
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
682