Chromatin-Bound IκBα Regulates a Subset of Polycomb Target Genes in Differentiation and Cancer

被引：43

作者：

Carmen Mulero, Maria ^{[1
]}

Ferres-Marco, Dolors ^{[2
]}

Islam, Abul ^{[3
,4
]}

Margalef, Pol ^{[1
]}

Pecoraro, Matteo ^{[5
]}

Toll, Agustti ^{[6
]}

Drechsel, Nils ^{[8
,9
]}

Charneco, Cristina ^{[8
,9
]}

Davis, Shelly ^{[10
]}

Bellora, Nicolas ^{[3
]}

Gallardo, Fernando ^{[6
]}

Lopez-Arribillaga, Erika ^{[1
]}

Asensio-Juan, Elena ^{[1
]}

Rodilla, Veronica ^{[1
]}

Gonzalez, Jessica ^{[1
]}

Iglesias, Mar ^{[7
]}

Shih, Vincent

Alba, M. Mar ^{[3
,12
]}

Di Croce, Luciano ^{[5
,12
]}

Hoffmann, Alexander ^{[11
]}

Miyamoto, Shigeki

Villa-Freixa, Jordi ^{[8
,9
,13
]}

Lopez-Bigas, Nuria ^{[12
]}

Keyes, William M. ^{[5
]}

Dominguez, Maria ^{[2
]}

Bigas, Anna ^{[1
]}

Espinosa, Lluis ^{[1
]}

机构：

[1] Inst Hosp Mar Invest Med IMIM, Program Canc Res, Barcelona 08003, Spain

[2] CSIC UMH, Inst Neurociencias Alicante, Alicante 03550, Spain

[3] Univ Pompeu Fabra, IMIM Hosp Mar, Res Program Biomed Informat, Barcelona 08003, Spain

[4] Univ Dhaka, Dept Genet Engn & Biotechnol, Dhaka 1000, Bangladesh

[5] CRG, Barcelona 08003, Spain

[6] Hosp del Mar, Dept Dermatol, Barcelona 08003, Spain

[7] Hosp del Mar, Dept Pathol, Barcelona 08003, Spain

[8] IMIM Hosp Mar, Computat Biochem & Biophys Lab, Barcelona 08003, Spain

[9] Univ Pompeu Fabra, Barcelona 08003, Spain

[10] Univ Wisconsin, Wisconsin Inst Med Res, Carbone Canc Ctr, McArdle Lab Canc Res, Madison, WI 53705 USA

[11] UCSD, Signaling Syst Lab, La Jolla, CA 92093 USA

[12] ICREA, Barcelona 08003, Spain

[13] Univ Vic, EPS, Barcelona 08500, Spain

来源：

CANCER CELL | 2013年 / 24卷 / 02期

关键词：

SQUAMOUS-CELL CARCINOMAS; NUCLEAR EXPORT SIGNAL; TRANSCRIPTIONAL REPRESSION; STEM-CELLS; EXPRESSION; ACTIVATION; DROSOPHILA; SKIN; ACETYLATION; COMPLEX;

D O I：

10.1016/j.ccr.2013.06.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

I kappa B proteins are the primary inhibitors of NF-kappa B. Here, we demonstrate that sumoylated and phosphorylated I kappa B alpha accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound I kappa B alpha modulates Polycomb recruitment and imparts their competence to be activated by TNF alpha. Mutations in the Drosophila I kappa B alpha gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-kappa B. Oncogenic transformation of keratinocytes results in cytoplasmic I kappa B alpha translocation associated with a massive activation of Hox. Accumulation of cytoplasmic I kappa B alpha was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation.

引用

页码：151 / 166

页数：16

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