Page last updated: 2024-10-24

SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, with ubiquitin-protein ligation catalyzed by an SCF (Skp1/Cul1/F-box protein) complex, and mediated by the proteasome. [PMID:15380083]

The SCF-dependent proteasomal ubiquitin-dependent protein catabolic process is a crucial cellular mechanism that selectively degrades proteins, playing a vital role in regulating numerous biological processes. This intricate process involves a multi-step cascade that begins with the recognition and tagging of target proteins with ubiquitin chains, followed by their delivery to the proteasome for degradation.

**1. Target Recognition and Ubiquitination:**

- SCF (Skp1-Cullin-F-box) complexes are E3 ubiquitin ligases that recognize specific target proteins through their F-box protein subunits.
- F-box proteins act as adaptors, binding to phosphorylated or modified target proteins, enabling the SCF complex to recruit them for ubiquitination.
- Once bound, the SCF complex recruits an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin molecules from an E1 ubiquitin-activating enzyme to the target protein.
- This process results in the sequential attachment of ubiquitin molecules to form a polyubiquitin chain on the target protein, specifically a Lys48-linked chain.

**2. Proteasomal Degradation:**

- Polyubiquitylated proteins are recognized and delivered to the 26S proteasome, a multi-protein complex responsible for protein degradation.
- The proteasome is composed of two major subunits:
- The 20S core particle, a cylindrical structure containing proteolytic sites.
- The 19S regulatory particle, responsible for recognizing polyubiquitylated proteins and unfolding them for entry into the 20S core.
- The polyubiquitin chain is removed, and the target protein is unfolded and translocated into the 20S core.
- Within the proteasome, the target protein is degraded into small peptides, which are then released into the cytoplasm for further processing or degradation.

**3. Regulation and Importance:**

- SCF-dependent ubiquitination is tightly regulated by phosphorylation, dephosphorylation, and other post-translational modifications.
- This regulation ensures the precise control of protein degradation, allowing cells to adapt to changing conditions and maintain homeostasis.
- This process is essential for cell cycle progression, signal transduction, DNA repair, and other fundamental cellular processes.
- Dysregulation of SCF-dependent ubiquitination can lead to various diseases, including cancer and neurodegenerative disorders.'
"

Proteins (1)

ProteinDefinitionTaxonomy
S-phase kinase-associated protein 2An S-phase kinase-associated protein 2 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
8-(4-tolylsulfonylamino)quinoline8-(4-tolylsulfonylamino)quinoline: has diabetogenic properties; can be used for fluorometric determination of zinc; structure given in first sourcesulfonamide
nsc 680410NSC 680410: a bcr/abl kinase inhibitor; structure in first source