Author
Listed:
- Jian Chen
(The University of Texas MD Anderson Cancer Center
Present address: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA)
- Ji-Hyun Shin
(The University of Texas MD Anderson Cancer Center)
- Ruiying Zhao
(The University of Texas MD Anderson Cancer Center)
- Liem Phan
(The University of Texas MD Anderson Cancer Center)
- Hua Wang
(The University of Texas MD Anderson Cancer Center)
- Yuwen Xue
(The University of Texas MD Anderson Cancer Center)
- Sean M. Post
(The University of Texas MD Anderson Cancer Center)
- Hyun Ho Choi
(The University of Texas MD Anderson Cancer Center)
- Jiun-Sheng Chen
(The University of Texas MD Anderson Cancer Center)
- Edward Wang
(The University of Texas MD Anderson Cancer Center)
- Zhongguo Zhou
(The University of Texas MD Anderson Cancer Center)
- Chieh Tseng
(The University of Texas MD Anderson Cancer Center)
- Christopher Gully
(The University of Texas MD Anderson Cancer Center)
- Guermarie Velazquez-Torres
(The University of Texas MD Anderson Cancer Center)
- Enrique Fuentes-Mattei
(The University of Texas MD Anderson Cancer Center)
- Giselle Yeung
(The University of Texas MD Anderson Cancer Center)
- Yi Qiao
(The University of Texas MD Anderson Cancer Center)
- Ping-Chieh Chou
(The University of Texas MD Anderson Cancer Center)
- Chun-Hui Su
(The University of Texas MD Anderson Cancer Center)
- Yun-Chih Hsieh
(The University of Texas MD Anderson Cancer Center)
- Shih-Lan Hsu
(Taichung Veterans General Hospital, No. 160, Section 3, Chung-Gang Road, Taichung, 40705 Taiwan, ROC)
- Kazufumi Ohshiro
(The University of Texas MD Anderson Cancer Center)
- Tattym Shaikenov
(The University of Texas MD Anderson Cancer Center)
- Huamin Wang
(The University of Texas MD Anderson Cancer Center)
- Sai-Ching Jim Yeung
(The University of Texas MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center)
- Mong-Hong Lee
(The University of Texas MD Anderson Cancer Center)
Abstract
Cullin-RING ubiquitin ligases (CRLs) are critical in ubiquitinating Myc, while COP9 signalosome (CSN) controls neddylation of Cullin in CRL. The mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is unclear. Here we show that Myc is a target of the CSN subunit 6 (CSN6)–Cullin signalling axis and that CSN6 is a positive regulator of Myc. CSN6 enhanced neddylation of Cullin-1 and facilitated autoubiquitination/degradation of Fbxw7, a component of CRL involved in Myc ubiquitination, thereby stabilizing Myc. Csn6 haplo-insufficiency decreased Cullin-1 neddylation but increased Fbxw7 stability to compromise Myc stability and activity in an Eμ-Myc mouse model, resulting in decelerated lymphomagenesis. We found that CSN6 overexpression, which leads to aberrant expression of Myc target genes, is frequent in human cancers. Together, these results define a mechanism for the regulation of Myc stability through the CSN–Cullin–Fbxw7 axis and provide insights into the correlation of CSN6 overexpression with Myc stabilization/activation during tumorigenesis.
Suggested Citation
Jian Chen & Ji-Hyun Shin & Ruiying Zhao & Liem Phan & Hua Wang & Yuwen Xue & Sean M. Post & Hyun Ho Choi & Jiun-Sheng Chen & Edward Wang & Zhongguo Zhou & Chieh Tseng & Christopher Gully & Guermarie V, 2014.
"CSN6 drives carcinogenesis by positively regulating Myc stability,"
Nature Communications, Nature, vol. 5(1), pages 1-15, December.
Handle:
RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6384
DOI: 10.1038/ncomms6384
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