IκB kinase ε phosphorylates TRAF2 to promote mammary epithelial cell transformation

Rhine R Shen; Alicia Y Zhou; Eejung Kim; Elgene Lim; Hasem Habelhah; William C Hahn

doi:10.1128/MCB.00468-12

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IκB kinase ε phosphorylates TRAF2 to promote mammary epithelial cell transformation

Journal article

Peer reviewed

IκB kinase ε phosphorylates TRAF2 to promote mammary epithelial cell transformation

Rhine R Shen, Alicia Y Zhou, Eejung Kim, Elgene Lim, Hasem Habelhah and William C Hahn

Molecular and cellular biology, Vol.32(23), pp.4756-4768

12/2012

DOI: 10.1128/MCB.00468-12

PMCID: PMC3497603

PMID: 23007157

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Abstract

NF-κB transcription factors are central regulators of inflammation and when dysregulated contribute to malignant transformation. IκB kinase ε (IKKε; IKKi, encoded by IKBKE) is a breast oncogene that is amplified in 30% of breast cancers and drives transformation in an NF-κB-dependent manner. Here we demonstrate that IKKε interacts with and phosphorylates tumor necrosis factor receptor-associated factor 2 (TRAF2) at Ser11 in vitro and in vivo. This activity promotes Lys63-linked TRAF2 ubiquitination and NF-κB activation and is essential for IKKε transformation. Breast cancer cells that depend on IKKε expression for survival are also dependent on TRAF2. This work defines TRAF2 phosphorylation to be one key effector of IKKε-induced mammary epithelial cell transformation.

Phosphorylation

NIH 3T3 Cells

Epithelial Cells - metabolism

Breast Neoplasms - immunology

Humans

NF-kappa B - immunology

Breast - metabolism

Breast Neoplasms - metabolism

Ubiquitination

Cysteine Endopeptidases - metabolism

I-kappa B Kinase - metabolism

HEK293 Cells

TNF Receptor-Associated Factor 2 - chemistry

Female

Breast - pathology

Amino Acid Sequence

Breast - cytology

Nuclear Pore Complex Proteins - metabolism

Breast - immunology

Down-Regulation

TNF Receptor-Associated Factor 2 - metabolism

Epithelial Cells - pathology

Cell Transformation, Neoplastic - metabolism

Cell Transformation, Neoplastic - immunology

Animals

TNF Receptor-Associated Factor 2 - immunology

Breast Neoplasms - pathology

Cysteine Endopeptidases - genetics

Epithelial Cells - immunology

Cell Line, Tumor

I-kappa B Kinase - immunology

Mice

RNA-Binding Proteins - metabolism

Details

Title: Subtitle: IκB kinase ε phosphorylates TRAF2 to promote mammary epithelial cell transformation
Creators: Rhine R Shen - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Alicia Y Zhou
Eejung Kim
Elgene Lim
Hasem Habelhah
William C Hahn
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.32(23), pp.4756-4768
DOI: 10.1128/MCB.00468-12
PMID: 23007157
PMCID: PMC3497603
NLM abbreviation: Mol Cell Biol
ISSN: 0270-7306
eISSN: 1098-5549
Publisher: United States
Grant note: R01 CA130988 / NCI NIH HHS P01 CA154303 / NCI NIH HHS F32 CA128265 / NCI NIH HHS R01 CA138475 / NCI NIH HHS
Language: English
Date published: 12/2012
Academic Unit: Pathology
Record Identifier: 9984047990502771

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