Related Experiment Video

Updated: Apr 8, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

14.0K

E3 ubiquitin ligase Cbl-b suppresses human ORMDL3 expression through STAT6 mediation

Wei-Xia Yang1, Rui Jin1, Chun-Ming Jiang2

  • 1Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.

FEBS Letters
|June 27, 2015
PubMed

Insights

Casitas B lineage lymphoma b (Cbl-b) suppresses Orosomucoid 1-Like Protein 3 (ORMDL3) expression in asthma. This mechanism involves Cbl-b reducing signal transducer and activator of transcription 6 (STAT6) phosphorylation, impacting airway immune tolerance.

Area of Science:

  • Immunology
  • Genetics

Background:

  • Orosomucoid 1-Like Protein 3 (ORMDL3) is implicated as an asthma candidate gene.
  • Casitas B lineage lymphoma b (Cbl-b), an E3 ubiquitin ligase, is crucial for airway immune tolerance.

Purpose of the Study:

  • To investigate the association between Cbl-b and ORMDL3 in asthma.
  • To elucidate the molecular mechanisms linking Cbl-b and ORMDL3 expression.

Main Methods:

  • Analysis of ORMDL3 expression and Cbl-b levels in peripheral blood of recurrent wheeze patients.
  • In vivo studies to determine Cbl-b's effect on ORMDL3 transcription.
  • Investigation of signal transducer and activator of transcription 6 (STAT6) phosphorylation in relation to interleukin 4 and Cbl-b.

Main Results:

  • ORMDL3 expression significantly increases with decreased Cbl-b in recurrent wheeze patients.
  • Cbl-b was found to suppress ORMDL3 transcriptional activity and mRNA expression.
  • Cbl-b reduced STAT6 phosphorylation, which is induced by interleukin 4 binding to the ORMDL3 promoter.

Conclusions:

  • Cbl-b suppresses human ORMDL3 expression via the STAT6 signaling pathway.
  • This finding provides a molecular link between Cbl-b and ORMDL3 in the context of asthma pathogenesis.
Keywords:
Casitas B lineage lymphoma bOrosomucoid 1-Like Protein 3Signal transducer and activator of transcription 6Transcriptional regulationWheeze

More Related Videos

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

3.3K
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

9.0K

Related Concept Videos

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...
3.0K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
14.0K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
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...
9.3K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.9K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.0K