Title |
IKKε-Mediated Tumorigenesis Requires K63-Linked Polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 Ubiquitin Ligase Complex
|
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Published in |
Cell Reports, February 2013
|
DOI | 10.1016/j.celrep.2013.01.031 |
Pubmed ID | |
Authors |
Alicia Y. Zhou, Rhine R. Shen, Eejung Kim, Ying J. Lock, Ming Xu, Zhijian J. Chen, William C. Hahn |
Abstract |
IκB kinase ε (IKKε, IKBKE) is a key regulator of innate immunity and a breast cancer oncogene, amplified in ~30% of breast cancers, that promotes malignant transformation through NF-κB activation. Here, we show that IKKε is modified and regulated by K63-linked polyubiquitination at lysine 30 and lysine 401. Tumor necrosis factor alpha and interleukin-1β stimulation induces IKKε K63-linked polyubiquitination over baseline levels in both macrophages and breast cancer cell lines, and this modification is essential for IKKε kinase activity, IKKε-mediated NF-κB activation, and IKKε-induced malignant transformation. Disruption of K63-linked ubiquitination of IKKε does not affect its overall structure but impairs the recruitment of canonical NF-κB proteins. A cIAP1/cIAP2/TRAF2 E3 ligase complex binds to and ubiquitinates IKKε. Altogether, these observations demonstrate that K63-linked polyubiquitination regulates IKKε activity in both inflammatory and oncogenic contexts and suggests an alternative approach to targeting this breast cancer oncogene. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 67% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 3% |
United States | 1 | 2% |
Sweden | 1 | 2% |
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Unknown | 58 | 92% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 11 | 17% |
Student > Bachelor | 5 | 8% |
Professor | 4 | 6% |
Student > Master | 4 | 6% |
Other | 12 | 19% |
Unknown | 8 | 13% |
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Other | 2 | 3% |
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