Related Experiment Video
Updated: Jun 3, 2026
09:40
In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
Published on: November 2, 2017
STRAP regulates c-Jun ubiquitin-mediated proteolysis and cellular proliferation.
Jennifer Reiner1, Fei Ye, Nilesh D Kashikar
1Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN, USA.
Biochemical and Biophysical Research Communications
|March 15, 2011
Summary
The WD40 protein STRAP regulates the stability of the c-Jun proto-oncogene. STRAP decreases c-Jun ubiquitylation and proteasomal degradation, impacting cell growth and tumorigenesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- STRAP (STRA6 P-interacting protein) is a WD40 protein linked to tumorigenesis.
- STRAP promotes oncogenic characteristics by activating ERK and pRb phosphorylation.
- The impact of STRAP on other MAPK pathways, particularly c-Jun regulation, remains unexplored.
Purpose of the Study:
- To investigate the role of STRAP in regulating the expression of the c-Jun proto-oncogene.
- To determine how STRAP influences c-Jun stability and degradation pathways.
- To assess the downstream effects of STRAP-mediated c-Jun regulation on cell growth and AP-1 activity.
Main Methods:
- Utilized STRAP knockout mouse embryonic fibroblasts (MEFs) and 293T cells.
- Assessed c-Jun protein and mRNA levels, phospho-c-Jun, c-Myc, and c-Fos expression.
- Investigated JNK activity, AP-1 target gene expression (cyclin D1), and cell growth.
- Examined c-Jun ubiquitylation and proteasomal degradation under conditions of proteasomal inhibition and STRAP overexpression.
Main Results:
- STRAP knockout MEFs showed reduced phospho-c-Jun and total c-Jun levels, but not c-Myc or c-Fos.
- STRAP deficiency decreased cyclin D1 expression and cell growth, with no change in JNK activity or basal c-Jun mRNA.
- Proteasomal inhibition rescued c-Jun expression in STRAP knockout MEFs; STRAP overexpression reduced c-Jun ubiquitylation and accelerated its turnover.
Conclusions:
- STRAP plays a critical role in regulating c-Jun proto-oncogene expression and stability.
- STRAP stabilizes c-Jun by inhibiting its ubiquitylation and subsequent proteasomal degradation.
- STRAP-mediated regulation of c-Jun impacts cell growth and holds implications for tumorigenesis.
More Related Videos
10:27Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Related Concept Videos
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
02:58Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
01:23Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...