Related Experiment Video
Updated: Jan 3, 2026
05:44
Utilization of Grafix for the Detection of Transient Interactors of Saccharomyces cerevisiae Spliceosome Subcomplexes
Published on: November 9, 2020
4.0K
SCF TrCP1 activates and ubiquitylates TAp63gamma
Jayme R Gallegos1, Joel Litersky1, Hunjoo Lee1
1Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239.
The Journal of Biological Chemistry
|October 30, 2007
Summary
The SCF(betaTrCP1) E3 ligase stabilizes and activates the p63 protein, a key player in epithelial differentiation and cancer. This interaction up-regulates p21, leading to cell cycle arrest, revealing a novel regulatory mechanism for p63.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- p63, a p53 family member, is crucial for epithelial differentiation and cancer progression.
- The precise molecular mechanisms regulating p63 activity are not fully understood.
Purpose of the Study:
- To identify the E3 ubiquitin ligase responsible for p63 regulation.
- To elucidate the role of this ligase in p63 function and downstream effects.
Main Methods:
- Co-immunoprecipitation to assess protein binding.
- Western blotting to detect protein levels and ubiquitylation.
- Quantitative PCR and promoter-luciferase assays to analyze gene expression and promoter binding.
Main Results:
- SCF(betaTrCP1) was identified as a unique E3 ubiquitin ligase for p63.
- SCF(betaTrCP1) binds and stabilizes TAp63gamma isoforms.
- Stabilized TAp63gamma up-regulates p21 expression, causing G1 phase cell cycle arrest.
- SCF(betaTrCP1) mediates TAp63gamma ubiquitylation, which is essential for its activation.
Conclusions:
- SCF(betaTrCP1) acts as an E3 ligase that activates p63 through ubiquitylation.
- This pathway represents a novel mechanism for p63 regulation with implications for cancer therapy.
More Related Videos
Related Concept Videos
01:45Tail-anchoring of Proteins in the ER Membrane
3.6K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.6K
00:50Anaphase Promoting Complex
3.3K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.3K
01:16TGF - β Signaling Pathway
10.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.3K
01:20Cotranslational Protein Translocation
9.4K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
9.4K
01:28Protein Translocation Machinery on the ER Membrane
6.4K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
6.4K
01:37The Unfolded Protein Response
6.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.1K