cellular response to topologically incorrect protein

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a protein that is not folded in its correct three-dimensional structure. [GOC:bf]

Cellular response to topologically incorrect protein is a complex process involving multiple cellular mechanisms aimed at detecting, correcting, or eliminating proteins that have misfolded or are incorrectly localized within the cell. These proteins can disrupt normal cellular function and lead to various pathologies. Here is a detailed description of the biological process:

**1. Detection of Misfolded Proteins:**
* **Chaperones:** Molecular chaperones such as Hsp70 and Hsp90 bind to misfolded proteins, preventing aggregation and providing an opportunity for refolding.
* **Ubiquitin Ligases:** Proteins with E3 ligase activity specifically recognize misfolded proteins and attach ubiquitin tags to them, marking them for degradation.
* **ER Stress Sensors:** In the endoplasmic reticulum (ER), specific sensors like IRE1, PERK, and ATF6 detect unfolded proteins, triggering the unfolded protein response (UPR).

**2. Protein Refolding:**
* **Chaperone-Mediated Refolding:** Chaperones attempt to refold misfolded proteins into their correct conformation.
* **ER-Associated Protein Degradation (ERAD):** If refolding fails, the misfolded protein is transported back to the cytoplasm for degradation via the proteasome.

**3. Protein Degradation:**
* **Proteasome:** The proteasome is a multi-protein complex that degrades ubiquitinated proteins into small peptides.
* **Autophagy:** This cellular process involves the engulfment and degradation of misfolded proteins and organelles within lysosomes.

**4. Signaling Pathways:**
* **Unfolded Protein Response (UPR):** This signaling pathway is activated by ER stress and aims to restore ER homeostasis by upregulating chaperones, inhibiting translation, and promoting ERAD.
* **p53 Pathway:** The tumor suppressor p53 can be activated by misfolded proteins, leading to cell cycle arrest, DNA repair, or apoptosis.

**5. Cellular Consequences:**
* **Cellular Stress:** Misfolded proteins can induce stress on the cell, leading to impaired cellular function and potential disease development.
* **Apoptosis:** If misfolded proteins overwhelm cellular repair mechanisms, programmed cell death (apoptosis) can be triggered to prevent further damage.
* **Disease Development:** The accumulation of misfolded proteins is implicated in various diseases, including neurodegenerative disorders (e.g., Alzheimer's, Parkinson's), cancer, and metabolic diseases.'
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Proteins (1)

Compounds (106)