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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2013 Jul 16

PMID 23850221

Citations 30

Authors

Maria Carmen Mulero

Dolors Ferres-Marco

Abul Islam

Pol Margalef

Matteo Pecoraro

Agusti Toll

Nils Drechsel

Cristina Charneco

Shelly Davis

Nicolas Bellora

Fernando Gallardo

Erika Lopez-Arribillaga

Elena Asensio-Juan

Veronica Rodilla

Jessica Gonzalez

Mar Iglesias

Vincent Shih

M Mar Alba

Luciano Di Croce

Alexander Hoffmann

Shigeki Miyamoto

Jordi Villa-Freixa

Nuria Lopez-Bigas

William M Keyes

Maria Dominguez

Anna Bigas

Lluis Espinosa

Affiliations

Soon will be listed here.

Abstract

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

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