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Implication of the ubiquitin/proteasome system in Myc-regulated transcription
Natalie von der Lehr1, Sara Johansson, Lars-Gunnar Larsson
1Department of Plant Biology and Forest Genetics, Uppsala Genetic Center, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Abstract:
The c-Myc oncoprotein is a transcription factor that controls genes involved in cell growth, apoptosis and oncogenesis. We and others recently showed that the F-box protein Skp2 interacts with c-Myc and participates in its ubiquitylation and proteasomal degradation. Surprisingly, Skp2 was also found to act as a positive cofactor for c-Myc-regulated transcription. Further, Skp2, ubiquitylated proteins and subunits of the proteasome were demonstrated to be associated with a c-Myc target promoter in vivo. We show here that c-Myc interacts with Skp2 as part of the SCFSkp2 E3 ubiquitin ligase complex. Further, c-Myc interacts with the Sug1, an AAA ATPase subunit of the 19S regulatory particle of the proteasome. Inhibition of Sug1 expression by siRNA reduced transcription from a Myc target promoter to the same extent as c-Myc or Skp2 siRNA, implicating Sug1in this process. Taken together these findings suggest a role of the ubiquitin/proteasome system in c-Myc-regulated transcription. A hypothetical model discussing the link between ubiquitylation and transcription will be presented.
Insights
The ubiquitin-proteasome system regulates transcription. Skp2 and Sug1, part of this system, interact with the c-Myc oncoprotein to control gene expression, impacting cell growth and oncogenesis.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- The c-Myc oncoprotein is a key transcription factor regulating cell growth, apoptosis, and oncogenesis.
- The F-box protein Skp2 interacts with c-Myc, mediating its ubiquitylation and proteasomal degradation.
- Skp2 also functions as a positive cofactor in c-Myc-regulated transcription, with Skp2, ubiquitylated proteins, and proteasome subunits found at c-Myc target promoters.
Purpose of the Study:
- To investigate the role of the ubiquitin/proteasome system in c-Myc-regulated transcription.
- To elucidate the interaction between c-Myc, Skp2, and proteasomal components in transcriptional regulation.
- To present a hypothetical model linking ubiquitylation and transcription.
Main Methods:
- Investigated the interaction of c-Myc with Skp2 within the SCFSkp2 E3 ubiquitin ligase complex.
- Examined the interaction between c-Myc and Sug1, an AAA ATPase subunit of the 19S proteasome regulatory particle.
- Utilized siRNA to inhibit Sug1 expression and assessed its impact on c-Myc target promoter transcription.
Main Results:
- Confirmed that c-Myc interacts with Skp2 as part of the SCFSkp2 E3 ubiquitin ligase complex.
- Demonstrated that c-Myc interacts with Sug1, a component of the proteasome's 19S regulatory particle.
- Showed that siRNA-mediated inhibition of Sug1 significantly reduced transcription from a Myc target promoter, similar to c-Myc or Skp2 inhibition.
Conclusions:
- The ubiquitin/proteasome system plays a crucial role in c-Myc-regulated transcription.
- Both Skp2 and Sug1 are implicated in the transcriptional control mediated by c-Myc.
- Findings support a functional link between ubiquitylation processes and transcriptional regulation by c-Myc.