Journal of Biomolecular Research & Therapeutics

Understanding the Impact of Protein Degradation on Cellular Health

Elle Casper^* Department of Genetic Engineering, University of Medical Sciences, Tehran, Iran
^*Correspondence: Elle Casper, Department of Genetic Engineering, University of Medical Sciences, Tehran, Iran, Email:

Received: 04-Oct-2023, Manuscript No. BOM-23-24143; Editor assigned: 06-Oct-2023, Pre QC No. BOM-23-24143(PQ); Reviewed: 23-Oct-2023, QC No. BOM-23-24143; Revised: 30-Oct-2023, Manuscript No. BOM-23-24143(R); Published: 06-Nov-2023, DOI: 10.35248/2167-7956.23.12.351

Description

Proteins are the molecular power of the cell, arranging diverse biological processes essential for life. However, the cell's dynamic environment necessitates a careful control over protein levels and functions. Protein degradation plays a pivotal role in maintaining cellular homeostasis, regulating cell cycle progression, and responding to environmental changes. This complex process involves the breakdown of proteins into their constituent amino acids, facilitating the recycling of valuable cellular resources and eliminating damaged or unnecessary proteins. In molecular biology, understanding the mechanisms of protein degradation has far-reaching implications, ranging from fundamental cellular processes to the development of targeted therapies for various diseases.

Ubiquitin-proteasome system

The Ubiquitin-Proteasome System (UPS) stands out as the primary machinery for selective protein degradation in eukaryotic cells. This complex system involves a series of steps arranged by enzymes that tag proteins for degradation. Ubiquitin, a small protein, serves as the "tag" in this process. E1 enzymes activate ubiquitin, which is then transferred to E2 enzymes and finally attached to the target protein by E3 ligases. This ubiquitin chain serves as a signal for recognition by the proteasome, a large protein complex that unfolds and degrades the tagged protein. The proteasome is a barrel-shaped structure with proteolytic activities in its core. Proteins are guided into the proteasome's catalytic chamber, where they are unfolded and cleaved into small peptides. The efficiency and selectivity of the UPS are vital for cellular function, as aberrations in this system can lead to the accumulation of misfolded or damaged proteins, contributing to various diseases, including neurodegenerative disorders and cancer.

While the UPS predominantly targets short-lived and regulatory proteins, autophagy serves as a complementary pathway, eliminating long-lived proteins, organelles, and protein aggregates. Autophagy involves the formation of double-membrane vesicles called autophagosomes, which engulf cellular components destined for degradation. The autophagosomes fuse with lysosomes, forming auto lysosomes where the cargo is degraded by lysosome enzymes. Autophagy is a conserved process vital for cellular homeostasis, particularly during nutrient deprivation or stress conditions. Dysregulation of autophagy has been implicated in various diseases, including cancer, neurodegenerative disorders, and infectious diseases. Understanding the molecular mechanisms of autophagy provides insights into potential therapeutic strategies for these conditions.

Proteolytic enzymes and their regulation

The UPS and autophagy employ various proteases to execute protein degradation. In the UPS, the 26S proteasome comprises a 20S catalytic core and two 19S regulatory particles. The 19S particle recognizes and unfolds ubiquitinated proteins, allowing them to enter the 20S core for degradation. The 20S core harbors different proteolytic activities, including chymotrypsinlike, trypsin-like, and caspase-like activities, ensuring the degradation of a diverse range of substrates. Proteasome activity is tightly regulated, with several cellular mechanisms modulating its function. Post-translational modifications, such as phosphorylation and ubiquitination, play key roles in regulating the activity and substrate specificity of the proteasome. Additionally, various proteins, known as proteasome-associated factors, influence the assembly and function of the proteasome.

Autophagy relies on lysosomal proteases for the degradation of engulfed cargo. Cathepsins, a family of lysosomal proteases, play a essential role in breaking down proteins within autolysosomes. The regulation of lysosomal function is complex and involves the coordination of lysosomal biogenesis, fusion with autophagosomes, and enzymatic activation. Defects in lysosomal function can lead to the accumulation of undegraded material and contribute to the pathogenesis of lysosomal storage disorders.

Protein degradation is complexly interlaced into various cellular processes, contributing to the regulation of cell cycle progression, signal transduction, and responses to cellular stress. The cell cycle, a highly regulated series of events that imperative cell division ensure the progression through different phases. The UPS targets key cell cycle regulators, such as cyclins and cyclin-dependent kinase inhibitors, arranging the precise transitions between cell cycle phases. Moreover, protein degradation plays a pivotal role in signal transduction pathways. The UPS regulates the abundance of signaling molecules by selectively targeting them for degradation. For instance, the degradation of IκB by the UPS is vital for the activation of the nuclear factor-kappa B (NF-κB) pathway, a central player in immune responses and inflammation. In stress responses, such as the Unfolded Protein Response (UPR) and the heat shock response, protein degradation mechanisms are activated to maintain cellular homeostasis. The UPR, triggered by the accumulation of misfolded proteins in the endoplasmic reticulum, up regulates the expression of chaperones and activates the UPS to alleviate protein folding stress. Similarly, the heat shock response induces the expression of heat shock proteins, which assist in protein folding and degradation during elevated temperatures.

Dysregulation of protein degradation pathways is implicated in various diseases. Neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's diseases, are characterized by the accumulation of misfolded proteins and protein aggregates. The failure of the UPS and autophagy to efficiently clear these aberrant proteins contributes to neuro degeneration. In cancer, the UPS is often seized to promote the degradation of tumor suppressors or the stabilization of onco proteins.

Protein degradation is a fundamental process in molecular biology, vital for maintaining cellular homeostasis, regulating cell cycle progression, and responding to environmental changes. The UPS and autophagy represent the major pathways orchestrating selective protein degradation, and their complex regulation is essential for cellular function. Dysregulation of protein degradation is implicated in various diseases, including neurodegenerative disorders and cancer, making it a promising target for therapeutic intervention. Advances in our understanding of protein degradation mechanisms have for the development of targeted therapies, exemplified by the success of proteasome inhibitors in cancer treatment. As research continues the complexities of protein degradation in molecular biology, new therapeutic strategies are likely to emerge, for the treatment of a wide array of diseases.