positive regulation of ERAD pathway

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of ERAD pathway. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie]

The ERAD pathway, short for Endoplasmic Reticulum-Associated Degradation, is a crucial quality control system for protein folding in the endoplasmic reticulum (ER). It is a tightly regulated process that ensures proper protein folding and removes misfolded or unassembled proteins from the ER lumen. Positive regulation of the ERAD pathway involves a cascade of events that enhance the identification, extraction, and degradation of misfolded proteins.

The initial step involves the recognition of misfolded proteins by chaperones like BiP, calnexin, and calreticulin. These chaperones assist in the proper folding of proteins and prevent aggregation. However, when a protein fails to fold correctly, these chaperones can also act as sensors, initiating the ERAD pathway.

Once a misfolded protein is recognized, it is ubiquitinated, a process involving the attachment of a ubiquitin molecule. This ubiquitination tag serves as a signal for the ERAD machinery to extract the misfolded protein from the ER lumen. The extraction is facilitated by a complex of proteins known as the ERAD translocon, which acts as a protein channel.

The ubiquitinated protein is then transferred to the cytoplasm, where it is degraded by the proteasome. The proteasome is a large protein complex responsible for breaking down misfolded or damaged proteins. This proteolytic activity ensures that misfolded proteins are eliminated, preventing their accumulation and potential toxicity.

Factors that positively regulate the ERAD pathway include:

* **Increased levels of chaperones**: Higher concentrations of chaperones like BiP enhance the recognition and binding of misfolded proteins.
* **Increased activity of ubiquitin ligases**: These enzymes promote the attachment of ubiquitin to misfolded proteins, marking them for degradation.
* **Activation of transcription factors**: Stress-responsive transcription factors, such as ATF6 and XBP1, can upregulate the expression of ERAD components, enhancing the pathway's efficiency.
* **Post-translational modifications**: Modifications like phosphorylation can regulate the activity of ERAD components, fine-tuning the pathway.

In summary, positive regulation of the ERAD pathway is essential for maintaining proper protein folding within the ER and ensuring the removal of misfolded proteins to prevent cellular dysfunction and stress.'
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Proteins (2)

Compounds (23)