HOME HELP FEEDBACK HOW TO CITE ABSTRACTS ARCHIVE CME INFORMATION SEARCH Cancer Research Clinical Cancer Research Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics Molecular Cancer Research Cancer Prevention Research Cancer Prevention Journals Portal Cancer Reviews Online Annual Meeting Education Book Meeting Abstracts Online		QUICK SEARCH:   [advanced] Author: Keyword(s):

Services Similar articles in this journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nishi, M. Articles by Ryo, A. Search for Related Content PubMed Articles by Nishi, M. Articles by Ryo, A.

Preclinical Studies and Early Drug Development: In Vitro and In Vivo Assays and Models

Role of the prolyl-isomerase Pin1 in cap-dependent translation and cell transformation

Yokohama City University School of Medicine, Yokohama, Japan

Abstract

B9

Cap-dependent translation is a fundamental process of gene expression and plays a critical role in cell proliferation and oncogenesis. Cap-dependent translation is initiated by the assembly of the eukaryotic translation initiation factors, eIF4E, eIF4G and eIF4A to form the eIF4F complex, which is often dysregulated in many human malignancies. eIF4E is abnormally highly expressed in multiple human cancers including breast cancer and the overexpression of eIF4E alone can transform mammary epithelial cells. Recent reports also indicate that eIF4E is regulated by specific post-translational modifications such as phosphorylation. However, the subsequent biological effects following phosphorylation have not yet been characterized. We here report that the peptidyl prolyl-isomerase Pin1 regulates eIF4E activation in breast cancer cells. The use of 7-methyl-GTP pull-down analysis reveals that Pin1 is present in eIF4E complexes specifically in breast cancer cells. Pin1 directly binds eIF4E via its Thr9-Pro and Thr11-Pro motifs, and enhances the interaction of both eIF4E and eIF4G with 7-methyl-GTP, thereby facilitating cap-dependent translation. Moreover, the depletion of Pin1 by specific siRNA significantly suppresses eIF4E-mediated cell transformation. These results indicate that Pin1 plays a pivotal role in the inappropriate activation of translational regulation via eIF4E in breast cancer cells, which affects both cell proliferation and oncogenic transformation. Hence, Pin1 could be an intriguing anti-cancer target.