XIAP-associated factor 1 interacts with and attenuates the trans-activity of four and a Half LIM protein 2

V. P. Tan , C. S. Lam , J. Wang , B. C. Wong , W. Zhang , Y. Yang , B. Jiang , J. Peng , S. Tu , C. Sardet (1) , Y. Zhang , R. Pang , I. F. Hung

1 IGMM - Institut de Génétique Moléculaire de Montpellier

XIAP-associated factor 1(XAF1) is a tumor suppressor with its functional mechanisms not fully understood. The zinc-finger cluster located at the N-terminus is the only domain structure. Four and a half LIM domain protein 2 (FHL2) also contains a tandem zinc finger structure, and its protein functions as an important adaptor and modifier in protein-protein interactions. Both of their structures are relatively simple, while the association between them is still unclear. In this study, we detected the interaction between XAF1 and FHL2 by using the yeast two-hybrid system. We identified FHL2 as a XAF1 binding protein. Furthermore, both XAF1 and FHL2 localized to the cytoplasm, mitochondria, and nucleus of gastric cancer cells. Over-expression of XAF1 excluded FHL2 from the nucleus and suppressed the trans-activity of FHL2 in stimulating the transcriptional activities of beta-catenin and AP-1. In conclusion, our findings unraveled an antagonistic mechanism between a tumor suppressor and an oncoprotein in cancer cells.

Mots clés: Genetic Protein Binding RNA; Cultured Two-Hybrid System Techniques beta Catenin/genetics/metabolism; Blotting; Genetic Transcriptional Activation Tumor Cells; Small Interfering/genetics Stomach Neoplasms/*genetics/metabolism/pathology *Trans-Activators Transcription Factor AP-1/genetics/metabolism Transcription Factors/*genetics/*metabolism Transcription; Western Cell Nucleus/metabolism Cytoplasm/metabolism Fluorescent Antibody Technique Homeodomain Proteins/*genetics/*metabolism Humans Immunoprecipitation Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/genetics/*metabolism Luciferases/metabolism Mitochondria/metabolism Muscle Proteins/*genetics/*metabolism Neoplasm Proteins/antagonists & inhibitors/genetics/*metabolism Promoter Regions

Domaines: Biochimie, Biologie Moléculaire

V. P. Tan, C. S. Lam, J. Wang, B. C. Wong, W. Zhang, et al.. XIAP-associated factor 1 interacts with and attenuates the trans-activity of four and a Half LIM protein 2. Molecular Carcinogenesis, 2011, 50 (3), pp.199--207. ⟨10.1002/mc.20705⟩. ⟨hal-02193331⟩