Page last updated: 2024-10-24

regulation of proteolysis

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of the hydrolysis of a peptide bond or bonds within a protein. [GOC:mah]

Proteolysis, the breakdown of proteins into smaller peptides or amino acids, is a fundamental biological process with crucial roles in a wide range of cellular functions. It is tightly regulated to ensure that proteins are degraded at the appropriate time and location, maintaining cellular homeostasis and responding to environmental cues. The regulation of proteolysis involves a complex interplay of factors, including:

**1. Ubiquitin-Proteasome System:** This is the major pathway for degrading intracellular proteins. It involves the attachment of ubiquitin, a small protein, to target proteins, marking them for degradation by the proteasome.

* **Ubiquitination:** A cascade of enzymes, including ubiquitin ligases (E3), attach ubiquitin molecules to lysine residues on target proteins.
* **Proteasome:** This large, multi-subunit complex recognizes and degrades polyubiquitinated proteins into short peptides.
* **Regulation of Ubiquitination:** Ubiquitin ligases exhibit high specificity and are regulated by various factors, including phosphorylation, cellular signaling pathways, and protein-protein interactions.

**2. Lysosomal Degradation:** This pathway targets proteins from the extracellular space, as well as misfolded or damaged proteins from within the cell.

* **Endocytosis and Autophagy:** These processes deliver proteins to lysosomes, which are acidic organelles containing hydrolytic enzymes.
* **Lysosomal Proteases:** These enzymes break down proteins into amino acids, which can be reused by the cell.
* **Regulation of Lysosomal Activity:** Lysosomal activity is regulated by factors like pH, the presence of specific substrates, and the activity of regulatory proteins.

**3. Regulated Intramembrane Proteolysis (RIP):** This pathway targets transmembrane proteins, often involved in signal transduction, by cleaving them within their transmembrane domain.

* **Specific Proteases:** RIP involves specialized proteases, such as γ-secretase, which cleave transmembrane proteins.
* **Signal Transduction:** RIP often triggers signaling cascades by releasing intracellular domains of transmembrane proteins, leading to changes in gene expression or cellular function.
* **Regulation of RIP:** The activity of RIP enzymes is tightly regulated by cellular signaling pathways and protein interactions.

**4. Other Proteolytic Systems:**

* **Caspases:** These proteases play critical roles in apoptosis, or programmed cell death, by degrading specific proteins involved in cell survival and maintenance.
* **Matrix Metalloproteinases (MMPs):** These enzymes degrade extracellular matrix proteins, playing roles in tissue remodeling, cell migration, and wound healing.

**In summary, the regulation of proteolysis is a dynamic and complex process essential for maintaining cellular homeostasis, responding to environmental cues, and regulating various cellular functions.**'
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Proteins (2)

ProteinDefinitionTaxonomy
NEDD8A NEDD8 protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15843]Homo sapiens (human)
Sonic hedgehog proteinA sonic hedgehog protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15465]Homo sapiens (human)

Compounds (6)

CompoundDefinitionClassesRoles
jervinejervine: teratogen from Veratrum grandiflorum; RN given refers to parent cpd(3beta,23beta)-isomer; structurepiperidines
cyclopaminepiperidinesglioma-associated oncogene inhibitor
cur 61414CUR 61414: inhibits the hedehog signaling pathway; structure in first source
pevonedistatpevonedistat : A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine which is substituted by a (1S)-2,3-dihydro-1H-inden-1-ylnitrilo group at position 4 and by a (1S,3S,4S)-3-hydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl group at position 7. It is a potent and selective NEDD8-activating enzyme inhibitor with an IC50 of 4.7 nM, and currently under clinical investigation for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes.

pevonedistat: a potent and selective inhibitor of NAE (NEDD8-activating enzyme)
cyclopentanols;
indanes;
pyrrolopyrimidine;
secondary amino compound;
sulfamidate
antineoplastic agent;
apoptosis inducer
gdc 0449HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activitybenzamides;
monochlorobenzenes;
pyridines;
sulfone
antineoplastic agent;
Hedgehog signaling pathway inhibitor;
SMO receptor antagonist;
teratogenic agent
robotnikininrobotnikinin: binds sonic hedgehog protein to block its signaling pathway; structure in first source