GO:0051603 obsolete proteolysis involved in protein catabolic process: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0051603 is an obsolete Gene Ontology biological process term that described the hydrolysis of peptide bonds within a protein as part of cellular protein breakdown.
• The term has been retired because its meaning is fully covered by more specific, active GO terms for proteolysis and protein catabolic process.
• Proteolysis involved in protein catabolism is essential for recycling amino acids, removing damaged proteins, and regulating short-lived regulatory proteins [1, 2].
• Key proteolytic systems include the ubiquitin-proteasome system and autophagy-lysosome pathways, both of which are conserved from plants to humans [1, 2, 5].
• Dysregulated proteolysis contributes to cardiovascular disease, lens cataract, peroxisome dysfunction, and impaired spermatogenesis [2, 4, 5, 6].
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable precise dissection of proteolytic gene function in disease and development [5, 6].
Description
GO:0051603, obsolete proteolysis involved in protein catabolic process, was a Gene Ontology biological process term that captured the hydrolysis of peptide bonds within a protein as part of the chemical reactions and pathways resulting in the breakdown of a protein by individual cells. It described a fundamental cellular activity: the controlled destruction of proteins into smaller peptides and amino acids, which is required for nutrient recycling, removal of misfolded or damaged proteins, and regulation of protein abundance [1, 2]. Although the term is now obsolete, the biology it represented remains central to cell biology, and researchers continue to study proteolysis in contexts such as autophagy, ubiquitin-dependent degradation, and organelle protein turnover [1, 2, 5].
obsolete proteolysis involved in protein catabolic process At A Glance
| GO ID | GO:0051603 |
|---|---|
| GO term | obsolete proteolysis involved in protein catabolic process |
| Ontology | biological_process |
| Synonym | peptidolysis during cellular protein catabolic process; peptidolysis during cellular protein catabolism; peptidolysis involved in cellular protein catabolic process; peptidolysis involved in cellular protein catabolism; proteolysis during cellular protein catabolic process; proteolysis during cellular protein catabolism; proteolysis involved in cellular protein catabolic process |
| Major function | Hydrolysis of peptide bonds within a protein as part of cellular protein breakdown |
| Status | Obsolete |
| Related processes | Autophagy, ubiquitin-proteasome system, organelle protein degradation |
| Relevant cellular contexts | Cytosol, lysosome, peroxisome, lens epithelium, germ cells |
What Is GO:0051603?
According to the QuickGO definition, GO:0051603 is OBSOLETE. It was defined as the hydrolysis of a peptide bond or bonds within a protein as part of the chemical reactions and pathways resulting in the breakdown of a protein by individual cells. In other words, it described the proteolytic step of cellular protein catabolism, where peptide bonds are cleaved to break a protein down into smaller fragments. The term has been retired because its meaning is now represented by more specific, active GO terms that separately describe proteolysis and protein catabolic process.
Why Is obsolete proteolysis involved in protein catabolic process Important in Cell Biology?
Proteolysis involved in protein catabolic process is important because it controls the lifetime and abundance of essentially every protein in a cell, thereby influencing development, stress responses, and disease [1, 2]. Defects in proteolytic pathways are linked to cardiovascular disorders, lens cataract, peroxisome dysfunction, and impaired spermatogenesis [2, 4, 5, 6]. Understanding this process at the gene and protein level is therefore essential for identifying therapeutic targets and for interpreting how cells maintain protein homeostasis [1, 2].
• Controls protein half-life and abundance, allowing rapid cellular responses to stress and developmental cues.
• Recycles amino acids during nutrient limitation through bulk and selective autophagy.
• Removes damaged or misfolded proteins that would otherwise be toxic.
• Regulates key signaling proteins via ubiquitin-dependent degradation [2, 6].
• Is essential for lens transparency; altered proteolysis contributes to cataract [4, 7].
• Supports peroxisome functional transitions through LON2 protease and autophagy [3, 5, 8].
• Plays a role in spermatogenesis through ubiquitination and proteolytic signaling.
• Provides targets for CRISPR-based functional studies in disease models [5, 6].
What Happens During obsolete proteolysis involved in protein catabolic process?
Substrate recognition and tagging
In simple terms: The cell first marks which proteins should be destroyed.
In many proteolytic pathways, substrate proteins are recognized and tagged, often by ubiquitination, before they are delivered to the degradation machinery [2, 6]. This tagging step provides specificity so that only selected proteins are broken down at a given time. In plant peroxisomes, matrix proteins are recognized for degradation during functional transitions, a process that involves chaperone and protease functions [5, 8].
Delivery to the proteolytic compartment
In simple terms: Tagged proteins are transported to the place where they will be cut apart.
Once tagged, proteins are delivered to proteolytic compartments such as the proteasome, lysosome, or peroxisome [1, 2]. Autophagy delivers bulk or selective cargo to the lysosome for degradation, serving as a master recycling pathway. In peroxisomes, matrix protein degradation depends on both peroxisome-associated proteases and autophagy-related routes [5, 8].
Peptide bond hydrolysis
In simple terms: Enzymes cut the protein into smaller pieces by breaking peptide bonds.
The defining chemical event of GO:0051603 is the hydrolysis of peptide bonds within a protein. This is carried out by proteases, including ubiquitin-dependent systems and lysosomal hydrolases [2, 7]. In bovine lens epithelial cells, a ubiquitin-dependent proteolysis system has been demonstrated, showing that peptide bond cleavage is tightly coupled to ubiquitin conjugation.
Release and reuse of degradation products
In simple terms: The breakdown products are recycled for new protein synthesis.
After hydrolysis, the resulting peptides and amino acids are released and reused by the cell. This recycling is especially important during nutrient stress, when autophagy provides amino acids for essential biosynthetic pathways. In the lens, proteolysis contributes to the turnover of crystallins and other proteins, and its dysregulation is associated with cataract formation [4, 7].
Coordination with signaling and quality control
In simple terms: Protein breakdown is coordinated with cell signaling and quality control.
Proteolysis is not merely a disposal system; it is integrated with signaling pathways that monitor protein quality and cellular state [2, 6]. Ubiquitination can serve both proteolytic and non-proteolytic signaling roles, as seen in spermatogenesis. In peroxisomes, the interplay between LON2 protease and autophagy ensures proper organelle function during developmental transitions [3, 8].
Key Genes Involved in GO:0051603 obsolete proteolysis involved in protein catabolic process
The following genes and proteins are representative components of proteolysis involved in protein catabolic process, based on published studies in autophagy, ubiquitin-dependent degradation, and organelle protein turnover.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ATG genes (autophagy-related) | Mediate bulk and selective autophagy for protein catabolism | Core machinery for recycling and stress responses |
| UBB / UBC | Ubiquitin precursors for protein tagging | Ubiquitin-dependent proteolysis in lens and other tissues |
| LON2 | Peroxisomal matrix protease | Peroxisome functional transition and protein degradation [5, 8] |
| LONP1 | Mitochondrial matrix protease | Mitochondrial protein quality control (contextual) |
| PSMA / PSMB subunits | Proteasome catalytic subunits | Ubiquitin-proteasome system in cardiovascular disease |
| SQSTM1/p62 | Selective autophagy receptor | Cargo recognition in autophagy |
| MAP1LC3B | Autophagosome marker | Autophagy flux measurement |
| CRYAA / CRYAB | Lens crystallins | Proteolysis and cataract biology [4, 7] |
| USP proteases | Deubiquitinating enzymes | Reversibility of ubiquitin-dependent proteolysis |
| E1 / E2 / E3 enzymes | Ubiquitin conjugation cascade | Specificity of substrate tagging [2, 6] |
| Cathepsins | Lysosomal proteases | Autophagy-lysosome degradation |
| BECN1 | Autophagy initiation | Autophagy regulation |
| ATG7 | Autophagy conjugation system | Autophagy-dependent protein catabolism |
| VCP/p97 | AAA-ATPase in protein quality control | Extraction of proteins for degradation |
| HSPA8/HSC70 | Chaperone | Chaperone-assisted proteolysis |
| RPN subunits | Proteasome regulatory particle | Substrate recognition by proteasome |
How Is obsolete proteolysis involved in protein catabolic process Regulated?
Proteolysis involved in protein catabolic process is regulated at multiple levels. Autophagy, a major route for bulk protein degradation, is controlled by nutrient-sensing pathways such as mTOR and by ATG gene products. Ubiquitin-dependent proteolysis is regulated by the coordinated action of E1, E2, and E3 enzymes, as well as deubiquitinating enzymes that remove ubiquitin from substrates [2, 6]. In peroxisomes, the LON2 protease and autophagy are dynamically regulated during functional transitions, ensuring that matrix proteins are degraded at the appropriate time [3, 5, 8]. In the lens, proteolytic activity is influenced by oxidative stress and aging, contributing to cataract formation [4, 7].
obsolete proteolysis involved in protein catabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ATG7 | Cardiovascular disease; autophagy deficiency | Knockout in cardiomyocytes |
| LON2 | Peroxisome dysfunction | Knockout in Arabidopsis [5, 8] |
| CRYAA | Cataract | Point mutation in lens epithelial cells [4, 7] |
| UBB | Impaired ubiquitin-dependent proteolysis | Overexpression in lens cells |
| VCP/p97 | Protein quality control disorders | Knock-in of disease mutations |
Cardiovascular disease
Autophagy and ubiquitination are critically involved in cardiovascular diseases, where altered proteolysis contributes to cardiomyocyte dysfunction and heart failure. Dysregulation of these pathways can lead to accumulation of damaged proteins and impaired cellular homeostasis.
Lens cataract
Proteolysis plays a central role in lens biology, and its dysregulation is associated with cataract formation. Bovine lens epithelial cells possess a ubiquitin-dependent proteolysis system, highlighting the importance of controlled protein breakdown for lens transparency.
Peroxisome-related disorders
Peroxisome-associated matrix protein degradation is essential for peroxisome function, and defects in this process can impair organelle transitions and cellular metabolism [5, 8]. The interplay between LON2 protease and autophagy is required for proper peroxisome dynamics [3, 8].
Spermatogenesis and reproductive biology
Protein ubiquitination and proteolysis have a subtle liaison with signaling during spermatogenesis, and disruptions can affect germ cell development. Both proteolytic and non-proteolytic roles of ubiquitination are important in this context.
From obsolete proteolysis involved in protein catabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of an autophagy gene impair protein catabolism? | CRISPR knockout in cell lines |
| Does a point mutation in a protease alter substrate cleavage? | CRISPR point mutation knock-in |
| Does tagging a protease affect its localization? | Tagged knock-in |
| Does overexpression of a ubiquitin gene enhance proteolysis? | Overexpression cell model |
| Which genes are essential for peroxisome protein degradation? | CRISPR library screening |
| How does a disease-associated mutation affect proteolytic flux? | Patient-derived iPSC knock-in |
How to Study the obsolete proteolysis involved in protein catabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Mass spectrometry proteomics | Protein and peptide abundance | Global protein catabolism profiling |
| LC3B flux assay | Autophagic degradation | Autophagy regulation studies |
| Ubiquitin conjugation assay | Ubiquitin-dependent proteolysis | Lens and cardiovascular models [2, 7] |
| Fluorogenic protease substrate | Protease activity | Proteasome and lysosome function |
| Confocal microscopy | Organelle dynamics | Peroxisome and lysosome imaging [3, 5] |
| CRISPR knockout screening | Gene essentiality for proteolysis | Pathway discovery |
| RNA-seq | Transcriptional changes | Stress and disease models |
| Western blot for p62 | Autophagic cargo turnover | Autophagy flux validation |
Proteomics and degradomics
Mass spectrometry-based proteomics can identify proteins and peptides generated during proteolysis, providing a global view of protein catabolism. Degradomics approaches specifically enrich for cleavage products to map protease substrates.
Autophagy flux assays
LC3B lipidation and p62 turnover are commonly used to monitor autophagic flux, a major route for proteolysis involved in protein catabolic process. These assays can be combined with CRISPR knockouts of ATG genes to test causality.
Ubiquitin-dependent degradation assays
Ubiquitin conjugation and proteasome activity can be measured using ubiquitin antibodies and fluorogenic substrates, as demonstrated in lens epithelial cells. Such assays help quantify the contribution of the ubiquitin-proteasome system to protein breakdown.
Imaging of proteolytic compartments
Fluorescence microscopy of lysosomes, autophagosomes, and peroxisomes allows visualization of proteolytic compartments and their dynamics [3, 5]. Tagged knock-in models enable tracking of specific proteases in live cells.
How CRISPR Can Be Used to Study GO:0051603 obsolete proteolysis involved in protein catabolic process
Knockout
CRISPR knockout of autophagy or proteasome genes can abolish specific proteolytic pathways, allowing researchers to test their contribution to protein catabolism [1, 5]. For example, knocking out ATG genes impairs bulk autophagy and affects peroxisome protein degradation.
Point Mutation
Point mutations in protease active sites or ubiquitin acceptor sites can be introduced to dissect catalytic mechanisms without fully deleting the gene [5, 8]. Such models are valuable for studying disease-associated variants in proteolytic genes.
Knock-in
Knock-in of tagged proteases or fluorescent reporters enables real-time tracking of proteolytic compartments and substrate flux. This approach is useful for studying LON2 dynamics and autophagy in living cells [3, 8].
Overexpression
Overexpression of ubiquitin or proteases can enhance proteolytic capacity and reveal rate-limiting steps in protein catabolism. This strategy has been used in lens epithelial cells to study ubiquitin-dependent proteolysis.
How EDITGENE Supports obsolete proteolysis involved in protein catabolic process Research
Researchers studying obsolete proteolysis involved in protein catabolic process-related genes often need to determine whether a candidate gene is causally involved in protein breakdown, whether a specific mutation alters protease activity, or whether overexpression changes cellular degradation capacity. EDITGENE provides the CRISPR tools and services to answer these questions with publication-grade precision.
Contact EDITGENE today to design your custom CRISPR model for obsolete proteolysis involved in protein catabolic process research.
Frequently Asked Questions About obsolete proteolysis involved in protein catabolic process
What is GO:0051603?
GO:0051603 is an obsolete Gene Ontology biological process term that described the hydrolysis of peptide bonds within a protein as part of cellular protein breakdown.
Why is GO:0051603 obsolete?
It is obsolete because its meaning is now covered by more specific, active GO terms for proteolysis and protein catabolic process.
What genes are involved in proteolysis involved in protein catabolic process?
Key genes include ATG autophagy genes, ubiquitin genes such as UBB and UBC, the peroxisomal protease LON2, and proteasome subunits [1, 2, 5, 7].
How is proteolysis involved in protein catabolic process regulated?
It is regulated by nutrient-sensing pathways such as mTOR, by ubiquitin conjugation and deubiquitination, and by organelle-specific proteases like LON2 [1, 2, 5, 8].
What diseases are linked to defective protein catabolism?
Defective protein catabolism is linked to cardiovascular disease, lens cataract, peroxisome dysfunction, and impaired spermatogenesis [2, 4, 5, 6].
What is the role of autophagy in protein catabolism?
Autophagy is a master pathway for bulk and selective recycling of proteins and organelles, delivering cargo to lysosomes for degradation.
How can CRISPR be used to study proteolysis?
CRISPR knockout, point mutation, knock-in, and overexpression models allow precise manipulation of proteolytic genes to test their function [5, 6, 7, 8].
What methods measure protein catabolism?
Proteomics, autophagy flux assays, ubiquitin conjugation assays, and imaging of proteolytic compartments are commonly used [1, 2, 7].
Is ubiquitin-dependent proteolysis important in the lens?
Yes, bovine lens epithelial cells have a ubiquitin-dependent proteolysis system, and its dysregulation is associated with cataract [4, 7].
What is the connection between peroxisomes and protein catabolism?
Peroxisome matrix protein degradation involves both LON2 protease and autophagy during functional transitions [3, 5, 8].
Conclusion
GO:0051603 obsolete proteolysis involved in protein catabolic process represents a fundamental cellular activity that remains highly relevant despite the term being retired. The hydrolysis of peptide bonds during protein breakdown is essential for recycling, quality control, and regulation, and its dysregulation contributes to cardiovascular disease, cataract, peroxisome dysfunction, and reproductive defects [1, 2, 4, 5, 6]. Modern CRISPR models and proteomics methods now allow researchers to dissect these pathways with unprecedented precision, making this an exciting area for both basic and translational research [5, 6, 7, 8].
References
- 1. Marshall RS et al.. 2018. Autophagy: The Master of Bulk and Selective Recycling.. Annu Rev Plant Biol 69:173-208 PMID: 29539270
- 2. Martins-Marques T et al.. 2015. Autophagy and ubiquitination in cardiovascular diseases.. DNA Cell Biol 34(4):243-51 PMID: 25602806
- 3. Goto-Yamada S et al.. 2015. Dynamics of the Light-Dependent Transition of Plant Peroxisomes.. Plant Cell Physiol 56(7):1264-71 PMID: 26063394
- 4. David LL et al.. 1989. Role of proteolysis in lenses: a review.. Lens Eye Toxic Res 6(4):725-47 PMID: 2562121
- 5. Burkhart SE et al.. 2013. Genetic dissection of peroxisome-associated matrix protein degradation in Arabidopsis thaliana.. Genetics 193(1):125-41 PMID: 23150599
- 6. Berruti G. 2021. Destruction or Reconstruction: A Subtle Liaison between the Proteolytic and Signaling Role of Protein Ubiquitination in Spermatogenesis.. Adv Exp Med Biol 1288:215-240 PMID: 34453739
- 7. Huang LL et al.. 1993. Bovine lens epithelial cells have a ubiquitin-dependent proteolysis system.. Biochim Biophys Acta 1175(2):181-7 PMID: 8380340
- 8. Goto-Yamada S et al.. 2014. Interaction between chaperone and protease functions of LON2, and autophagy during the functional transition of peroxisomes.. Plant Signal Behav 9(5):e28838 PMID: 24739336
