Significant Protein Degradation Pathways to Know for Proteomics

Understanding significant protein degradation pathways is key in proteomics. These pathways, like the Ubiquitin-Proteasome System and autophagy, help regulate protein levels, maintain cellular health, and respond to stress, ensuring proper cellular function and homeostasis.

1. Ubiquitin-Proteasome System (UPS)

   • Involves tagging proteins with ubiquitin, signaling them for degradation.
   • The proteasome is a large complex that degrades ubiquitinated proteins into small peptides.
   • Plays a critical role in regulating protein levels, cell cycle, and responses to stress.

2. Autophagy-Lysosomal Pathway

   • A cellular process that degrades and recycles cellular components through lysosomes.
   • Involves the formation of autophagosomes that engulf damaged organelles or proteins.
   • Essential for maintaining cellular homeostasis and responding to nutrient deprivation.

3. Calpain-mediated Proteolysis

   • Calpains are calcium-dependent cysteine proteases that cleave specific proteins.
   • Involved in various cellular processes, including cell signaling and apoptosis.
   • Plays a role in muscle protein turnover and remodeling during stress.

4. Caspase-mediated Proteolysis

   • Caspases are a family of cysteine proteases that play a key role in apoptosis.
   • They cleave specific substrates, leading to programmed cell death and inflammation.
   • Involved in the degradation of cellular components during development and immune responses.

5. Endoplasmic Reticulum-Associated Degradation (ERAD)

   • A quality control mechanism that targets misfolded proteins in the endoplasmic reticulum for degradation.
   • Involves retrotranslocation of substrates from the ER to the cytosol for proteasomal degradation.
   • Critical for maintaining protein homeostasis and preventing accumulation of toxic proteins.

6. N-end Rule Pathway

   • A degradation pathway that recognizes the N-terminal residue of proteins to determine their stability.
   • Specific amino acids at the N-terminus can signal for ubiquitination and subsequent degradation.
   • Plays a role in regulating protein turnover in response to cellular conditions.

7. Mitochondrial Protein Degradation

   • Involves the selective degradation of damaged or unneeded mitochondrial proteins.
   • Mitochondria have their own proteases, such as Lon and ClpXP, for quality control.
   • Essential for mitochondrial function and preventing oxidative stress.

8. Heat Shock Protein-mediated Degradation

   • Heat shock proteins (HSPs) assist in the proper folding of proteins and prevent aggregation.
   • They can also target misfolded proteins for degradation through the proteasome or autophagy.
   • Play a crucial role in cellular stress responses and maintaining protein homeostasis.

9. Chaperone-mediated Autophagy (CMA)

   • A selective form of autophagy that degrades specific cytosolic proteins.
   • Involves chaperones recognizing target proteins and facilitating their transport to lysosomes.
   • Important for regulating protein quality and cellular responses to stress.

10. Sumoylation-dependent Protein Degradation

    • Involves the attachment of small ubiquitin-like modifier (SUMO) proteins to target proteins.
    • SUMOylation can signal for proteasomal degradation or alter protein function and localization.
    • Plays a role in various cellular processes, including stress responses and gene regulation.