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Skp2 Regulates Myc Protein Stability and Activity
Abstract
Myc is an oncoprotein transcription factor that plays a prominent role in cancer. Like many transcription factors, Myc is an unstable protein that is destroyed by ubiquitin (Ub)-mediated proteolysis. Here, we report that the oncoprotein and Ub ligase Skp2 regulates Myc ubiquitylation and stability. Because of the growing number of Ub ligases that function as transcriptional coactivators, we speculated that Skp2 might also regulate Myc's transcriptional activity. Consistent with this model, we also show that Skp2 is a transcriptional coactivator for Myc, recognizing an essential element within the Myc activation domain and activating Myc target genes. These data suggest that Skp2 functions to connect Myc activity and destruction, and reveal an unexpected oncoprotein connection that may play an important role in controlling cell growth in normal and cancer cells.
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“In fact, the Skp2 ubiquitin ligase is a coactivator of c-Myc at the cyclin D2 promoter and loss of Skp2 can stabilize c-Myc protein levels and reduce transactivation of c-Myc-responsive promoters (Kim et al. 2003; von der Lehr et al. 2003).”
From Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex (2004) · cites this paper as Kim et al. 2003
In the citing paper
“In fact, the Skp2 ubiquitin ligase is a coactivator of c-Myc at the cyclin D2 promoter and loss of Skp2 can stabilize c-Myc protein levels and reduce transactivation of c-Myc-responsive promoters (Kim et al. 2003; von der Lehr et al. 2003).”
From Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex (2004) · cites this paper as Kim et al. 2003
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Function and regulation of cullin–RING ubiquitin ligases
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Metadata
- Authors
- Kim, S. Y., Herbst, A., Tworkowski, K. A., Salghetti, S. E., & Tansey, W. P.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 11
- Issue
- 5
- Pages
- 1177-1188
- ISSN
- 1097-2765
- Cited by
- 440
- References
- 2
- Language
- en
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