Question

Proteins are degraded in cells. What is ubiquitin, and what role does it play in tagging proteins for degradation? What is the role of proteasomes in protein degradation? How might proteasome inhibitors serve as chemotherapeutic (cancer-treating) agents? 

Answer 1

The total proteins present in a cell varies according the rate of its syntheisis and degradation. There are certain pathways which help in degrading the proteins into amini acids. the resultant amino acids will be used for another function. The Ubiquitin Proteasome Pathway is one of the important protein degradation mechansim seen in cytosol and nucleus of eukaryotes which is highly conserved. It is useful in degrading proteins which are incomplete, misfolded or unnecessary proteins.

Ubiquitin is a polypeptide containing  76 amino acid mostly used as tag for selective protein degradation. Any protein marked with ubiquitin will be considered for protein degradation by proteasome. The process is called as ubiquitination or kiss of death process. A ubiquitin molecule which attaches to a protein recruits other ubiquitin for attaching, forming multiubiquitin chain. After the protein degradation, ubiquitins are released which can be used for tagging other proteins to be degraded. Ubiquitin binds to the lysine residue of the protein.

So ubiquitin is very important for the maintaining cell cycle, processing programmed cell death, protein activation and inactivation, protein interactions, etc.

Proteasomes are protease complexes, barrell shaped which degrades proteins ubiquinated through the lysine residue. They degrade proteins by breaking the peptide bonds, working as endoprotease. proteasome is a 26S unit complex (catalytic 20S core and the 19S regulator) which degrades the proteins through cascade of events.

Our body normally produces unwanted or non functional proteins such as misfolded ones or short lived ones or obsolete ones which is degraded and recycled by proteasome or completely degraded by lysosome. In case of cancer cells, the cell division is rapid and so the accumulation of unwanted proteins increases. IF proteasome is present, it will degrade the unwanted protein and increase the amino acid in the cell. SO proteasome inhibitors- molecules that inhibit proteasomes are used in myelome cancer, so that the unwanted proteins accumulates and after a limit, it gets completely degraded by the cell itself. This molecule can stop the accumulation of amino acids and thereby the unwanted proteins, thus used for cancer theraphy. They increases the sensitivity of cancer treatment on combining with other chemotherapeutic agents.

Proteosome