XIAP-associated Factor 1 Interacts With and Attenuates the Trans-Activity of Four and a Half LIM Protein 2

Mol Carcinog. 2011 Mar;50(3):199-207. doi: 10.1002/mc.20705. Epub 2010 Nov 23.

Abstract

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 β-catenin and AP-1. In conclusion, our findings unraveled an antagonistic mechanism between a tumor suppressor and an oncoprotein in cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • FHL2 protein, human
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIM-Homeodomain Proteins
  • Muscle Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Trans-Activators
  • Transcription Factor AP-1
  • Transcription Factors
  • XAF1 protein, human
  • beta Catenin
  • Luciferases