Emerging roles for the non-canonical IKKs in cancer

被引:115
作者
Shen, R. R. [1 ]
Hahn, W. C. [1 ,2 ]
机构
[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[2] Broad Inst Harvard & MIT, Cambridge, MA USA
关键词
NF-kappa B; cancer; IKK; NF-KAPPA-B; INNATE IMMUNE-RESPONSE; KINASE-RELATED KINASES; TUMOR-SUPPRESSOR CYLD; INTERFERON REGULATORY FACTOR-3; UBIQUITIN-LIKE DOMAIN; BREAST-CANCER; I INTERFERON; ANTIVIRAL RESPONSE; ADAPTER PROTEIN;
D O I
10.1038/onc.2010.493
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The I kappa B Kinase (IKK)-related kinases TBK1 and IKK epsilon have essential roles as regulators of innate immunity by modulating interferon and NF-kappa B signaling. Recent work has also implicated these non-canonical IKKs in malignant transformation. IKK epsilon is amplified in similar to 30% of breast cancers and transforms cells through the activation of NF-kappa B. TBK1 participates in RalB-mediated inflammatory responses and cell survival, and is essential for the survival of non-small cell lung cancers driven by oncogenic KRAS. The delineation of target substrates and downstream activities for TBK1 and IKK epsilon has begun to define their role(s) in promoting tumorigenesis. In this review, we will highlight the mechanisms by which IKKe and TBK1 orchestrate pathways involved in inflammation and cancer. Oncogene (2011) 30, 631-641; doi:10.1038/onc.2010.493; published online 1 November 2010
引用
收藏
页码:631 / 641
页数:11
相关论文
共 112 条
[31]   Inducible IκB kinase/IκB kinase ε expression is induced by CK2 and promotes aberrant nuclear factor-κB activation in breast cancer cells [J].
Eddy, SF ;
Guo, SQ ;
Demicco, EG ;
Romieu-Mourez, R ;
Landesman-Borag, E ;
Seldin, DC ;
Sonenshein, GE .
CANCER RESEARCH, 2005, 65 (24) :11375-11383
[32]   Oncogenic Ha-Ras-induced signaling activates NF-kappa B transcriptional activity, which is required for cellular transformation [J].
Finco, TS ;
Westwick, JK ;
Norris, JL ;
Beg, AA ;
Der, CJ ;
Baldwin, AS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (39) :24113-24116
[33]   IKKε and TBK1 are essential components of the IRF3 signaling pathway [J].
Fitzgerald, KA ;
McWhirter, SM ;
Faia, KL ;
Rowe, DC ;
Latz, E ;
Golenbock, DT ;
Coyle, AJ ;
Liao, SM ;
Maniatis, T .
NATURE IMMUNOLOGY, 2003, 4 (05) :491-496
[34]   Identification of NAP1, a regulatory subunit of IκB kinase-related kinases that potentiates NF-κB signaling [J].
Fujita, F ;
Taniguchi, Y ;
Kato, T ;
Narita, Y ;
Furuya, A ;
Ogawa, T ;
Sakurai, H ;
Joh, T ;
Itoh, M ;
Delhase, M ;
Karin, M ;
Nakanishi, M .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (21) :7780-7793
[35]   Lipopolysaccharide-mediated interferon regulatory factor activation involves TBK1-IKKε-dependent lys63-linked polyubiquitination and phosphorylation of TANK/I-TRAF [J].
Gatot, Jean-Stephane ;
Gioia, Romain ;
Chau, Tieu-Lan ;
Patrascu, Felicia ;
Warnier, Michael ;
Close, Pierre ;
Chapelle, Jean-Paul ;
Muraille, Eric ;
Brown, Keith ;
Siebenlist, Ulrich ;
Piette, Jacques ;
Dejardin, Emmanuel ;
Chariot, Alain .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (43) :31131-31146
[36]   New regulators of NF-κB in inflammation [J].
Ghosh, Sankar ;
Hayden, Matthew S. .
NATURE REVIEWS IMMUNOLOGY, 2008, 8 (11) :837-848
[37]   Roles of an IκB kinase-related pathway in human cytomegalovirus-infected vascular smooth muscle cells -: A molecular link in pathogen-induced proatherosclerotic conditions [J].
Gravel, SP ;
Servant, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (09) :7477-7486
[38]   NF-κB is a negative regulator of IL-1β secretion as revealed by genetic and pharmacological inhibition of IKKβ [J].
Greten, Florian R. ;
Arkan, Melek C. ;
Bollrath, Julia ;
Hsu, Li-Chung ;
Goode, Jason ;
Miething, Cornelius ;
Goktuna, Serkan I. ;
Neuenhahn, Michael ;
Fierer, Joshua ;
Paxian, Stephan ;
Van Rooijen, Nico ;
Xu, Yajun ;
O'Cain, Timothy ;
Jaffee, Bruce B. ;
Busch, Dirk H. ;
Duyster, Justus ;
Schmid, Roland M. ;
Eckmann, Lars ;
Karin, Michael .
CELL, 2007, 130 (05) :918-931
[39]   IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer [J].
Greten, FR ;
Eckmann, L ;
Greten, TF ;
Park, JM ;
Li, ZW ;
Egan, LJ ;
Kagnoff, MF ;
Karin, M .
CELL, 2004, 118 (03) :285-296
[40]   Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK [J].
Guo, Beichu ;
Cheng, Genhong .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (16) :11817-11826