alexa c-Jun N-terminal kinase (JNK1) upregulates XIAP-associated factor 1 (XAF1) through interferon regulatory factor 1 (IRF-1) in gastrointestinal cancer.
Molecular Biology

Molecular Biology

Journal of Cytology & Histology

Author(s): Wang J, Zhang W, Zhang Y, Chen Y, Zou B,

Abstract Share this page

Abstract BACKGROUND AND AIMS: X-linked inhibitor of apoptosis protein-associated factor 1 (XAF1) is a tumor suppressor that can sensitize cancer cell to apoptosis. Intrinsic expression of XAF1 in cancer cell is low. Our purpose is to determine the effect of c-Jun N-terminal kinase 1 (JNK1) on XAF1 expression and the putative mechanism. METHODS: XAF1 expression in gastrointestinal (GI) cancer cell line AGS and SW1116 was detected by reverse transcription-polymerase chain reaction (PCR), real-time PCR and immunoblotting. The role of JNK1 was assessed by ectopic overexpression with wild-type (JNK1-WT) and dominant-negative (JNK1-DN) JNK1 constructs. The effects of JNK1 activator, interferon (IFN)-alpha, tumor necrosis factor (TNF)-alpha and phorbol-12-myristate-13-acetate (PMA), or JNK1 inhibitor, SP600125, were evaluated. An XAF1 promoter reporter pLUC107 with WT or mutated interferon regulatory factor 1-binding element (IRF-E) was used to assess JNK1-induced transcription by dual luciferase assay. RESULT: Ectopic overexpression of JNK1-WT or treatment with IFN-alpha, TNF-alpha and PMA induced whereas SP600125 suppressed intrinsic and induced XAF1 expression. Induction of XAF1 required de novo protein synthesis. Moreover, JNK1 stimulated whereas SP600125 suppressed XAF1 promoter activity. JNK1 stimulated interferon regulatory factor 1 (IRF-1) expression, whereas both IRF-1 small-interfering RNA and site mutation of IRF-E within XAF1 promoter abrogated the effect of JNK1. CONCLUSION: JNK1 stimulated and mediated the effects of IFN and TNF-alpha on XAF1 expression through transcriptional regulation by induction of IRF-1. The linkage of JNK1, IRF-1 and XAF1 in the same signal pathway may unravel a novel mechanism in regulation of apoptosis and differentiation of GI cancers. This article was published in Carcinogenesis and referenced in Journal of Cytology & Histology

Relevant Expert PPTs

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords