38 Questions
Which enzymes are involved in the attachment of ubiquitin to the target protein?
E1, E2, E3, E4
What is the function of proteasomes in intracellular proteins?
Degradation of intracellular proteins
What is the attachment site to the target protein on ubiquitin?
C-terminus
How is proteolysis, the breakdown of proteins, achieved in general?
By the hydrolysis of the peptide bond
What is the structure of the 20S proteasome core complex?
Two identical outer α rings and two inner β rings
What are the catalytic sites associated with in the 20S proteasome core complex?
Specific β subunits
What is the average length of peptides produced by the proteasome?
7-9 amino acids
What happens to the polyubiquitinated protein in the 26S proteasome?
It is recognized, unfolded, and degraded
What is the initial association of the polyubiquitinated protein in the 19S complex?
Via the ubiquitin chain
What is the role of ubiquitination in cellular processes?
Involved in essential cellular processes such as cell-cycle progression, transcriptional activation, and apoptosis
What is the effect of ubiquitination on the C-terminal tail region of α-spectrin?
Down-regulates the affinity of spectrin-4.1a-actin and spectrin-adducin-actin ternary complexes
What cellular process does Wnt signaling depend on?
Steady-state levels of the multifunctional protein β-catenin
What genetic defect can result in Angelman syndrome?
Deletion of the E3 enzyme gene of the proteasome-ubiquitin system
What is the most common genetic defect leading to Angelman syndrome?
An ~4Mb maternal deletion in chromosomal region 15q11-13
Which E3 ligase is associated with Williams syndrome?
UBE3A
What is the function of Ataxin-3 (ATXN3) E3-ligase?
Interacts with ubiquitinated proteins and can interfere with the degradation of substrates
What is the role of Bortezomib?
First therapeutic proteasome inhibitor approved by FDA for treating relapsed multiple myeloma and mantle cell lymphoma
Which histone modification is considered a repressive mark?
H2A mono-ubiquitination
What is the cellular response to misfolded proteins when the capacity of the proteasome is exceeded?
Aggresomes
What is the function of Deubiquitinating enzymes (DUBs) in eukaryotic cells?
To remove ubiquitin from proteins
Which DUB is associated with Ataxia?
USP-14
What is the primary function of Small Ubiquitin-like Modifier (SUMO) proteins?
Involved in nuclear-cytosolic transport
Which disease is associated with UCH-L1 (PARK5)?
Parkinson disease
What is the function of the SCF complex?
Constitutes one of the four subunits of the ubiquitin protein ligase complex
What is the role of the E3 ligase, Parkin (PARK2)?
Associated with neurodegenerative diseases
What is the function of Endoplasmic-reticulum-associated protein degradation (ERAD)?
Targets misfolded proteins of ER for ubiquitination and subsequent degradation by proteasome
What is the role of Small Ubiquitin-like Modifier (SUMO) proteins?
Regulating nuclear-cytosolic transport
What is the function of Deubiquitinating enzymes (DUBs) in eukaryotic cells?
Cleaving ubiquitin from target proteins
Which E3 ligase is associated with Williams syndrome?
UBE3A
What is the cellular response to misfolded proteins when the capacity of the proteasome is exceeded?
Protein aggregation into aggresomes
What is the primary function of Ataxin-3 (ATXN3) E3-ligase?
Interacting with ubiquitinated proteins for degradation
What is the function of the SCF complex?
Targeting proteins for degradation
What is the effect of ubiquitination on the C-terminal tail region of $\alpha$-spectrin?
Enhancing protein degradation
What is the function of Bortezomib?
Inhibiting protein degradation
What is the role of ubiquitination in cellular processes?
Targeting proteins for degradation
What is the function of Endoplasmic-reticulum-associated protein degradation (ERAD)?
Targeting misfolded proteins for degradation
What is the role of Parkin (PARK2) E3-ligase?
Interacting with ubiquitinated proteins for degradation
What is the average length of peptides produced by the proteasome?
20-25 amino acids
Study Notes
Proteasome Structure and Function
- The 20S proteasome core complex has two identical outer α rings, two inner β rings, with each ring containing seven distinct subunits.
- Catalytic sites are associated with specific β subunits, with three of the β subunits having different substrate specificity.
- The poly-ubiquitinated protein is recognized by the 26S proteasome, unfolded, and degraded, with the ubiquitin molecules being recycled.
- The length of produced peptides ranges from 3 to 23 amino acids, with an average length of 7-9 amino acids, and the peptide composition of a given protein remains constant.
- Peptides produced by the proteasome are further degraded by other proteases and amino peptidases.
- The polyubiquitinated protein initially associates with the 19S complex via the ubiquitin chain, allowing entry into the 20S core complex for degradation into small peptides.
- Ubiquitination is involved in various essential cellular processes such as cell-cycle progression, transcriptional activation, and apoptosis.
- The molecular bases of the irreversibly sickled cell are related to posttranslational modifications in β actin and diminished ubiquitination of spectrin, leading to a "locked" membrane skeleton.
- Ubiquitination of the C-terminal tail region of α-spectrin down-regulates the affinity of spectrin-4.1a-actin and spectrin-adducin-actin ternary complexes.
- Wnt signaling depends on the steady-state levels of the multifunctional protein β-catenin, which is regulated by phosphorylation, ubiquitination, and degradation by the proteasome.
- Deletion of the E3 enzyme gene of the proteasome-ubiquitin system can result in Angelman syndrome, which can also be caused by mutation of the Ube3a gene, present on both maternal and paternal chromosomes with differing patterns of methylation.
- The most common genetic defect leading to Angelman syndrome is an ~4Mb maternal deletion in chromosomal region 15q11-13, causing an absence of Ube3a expression in the maternally imprinted brain regions.
Test your knowledge of the proteasome structure and function with this quiz. Explore topics such as polyubiquitination, peptide production, protein degradation, and the role of the proteasome-ubiquitin system in various cellular processes and genetic disorders.
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