Related Experiment Video

Updated: Mar 1, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

6.1K

Multiple functions of the E3 ubiquitin ligase CHIP in immunity

Shaohua Zhan1, Tianxiao Wang2, Wei Ge1

  • 1a Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , National Key Laboratory of Medical Molecular Biology & Department of Immunology , Dongcheng District , Beijing , China.

International Reviews of Immunology
|June 3, 2017
PubMed

Insights

The carboxyl terminal of Hsp70-interacting protein (CHIP) is an E3 ubiquitin ligase crucial for protein quality control. This review models CHIP

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • The carboxyl terminal of Hsp70-interacting protein (CHIP) functions as an E3 ubiquitin ligase, integral to the protein quality control system.
  • CHIP influences the balance between protein folding and degradation pathways, but its substrate selection mechanisms remain unclear.
  • CHIP's regulation of substrate protein levels impacts various physiological and pathological conditions, including cancer and neurological disorders.

Purpose of the Study:

  • To present a comprehensive model detailing CHIP's substrate degradation mechanisms, encompassing both chaperone-dependent and direct pathways.
  • To elucidate CHIP's role in regulating immune responses, including innate and adaptive immunity.
  • To explore the involvement of CHIP in immune-related diseases.

Main Methods:

  • This review synthesizes existing literature on CHIP function and regulation.
  • Mechanistic insights are derived from studies on protein ubiquitination and degradation pathways.
  • Information on CHIP's involvement in immunity is compiled from research on immune signaling and disease models.

Main Results:

  • A detailed model for CHIP-mediated substrate degradation is proposed, highlighting chaperone interactions.
  • CHIP's significant regulatory roles in diverse physiological processes, including immunity, are discussed.
  • The review identifies gaps in understanding CHIP's precise mechanisms in immune regulation.

Conclusions:

  • CHIP is a key regulator of protein homeostasis and cellular function, with critical roles in immunity.
  • Further research is needed to fully understand CHIP's intricate mechanisms in immune system modulation.
  • CHIP's dysregulation is implicated in various immune-related pathologies, suggesting therapeutic potential.

Keywords:
CHIPUbiquitinationchaperoneimmune systemsubstrate

More Related Videos

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination07:58

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

483
Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta10:27

Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta

Published on: December 5, 2019

9.4K

Related Concept Videos

Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
9.1K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.9K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.0K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.4K