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Updated: Jun 6, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
XIAP-associated factor 1 interacts with and attenuates the trans-activity of four and a Half LIM protein 2
Wenjing Zhang1, Yi Yang, Bo Jiang
1Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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.
Insights
XIAP-associated factor 1 (XAF1), a tumor suppressor, interacts with Four and a half LIM domain protein 2 (FHL2). XAF1 antagonizes FHL2
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- XIAP-associated factor 1 (XAF1) is a tumor suppressor whose functions are not fully understood.
- Four and a half LIM domain protein 2 (FHL2) is an adaptor protein involved in protein-protein interactions.
- The interaction between XAF1 and FHL2 remains unclear despite their simple structures.
Purpose of the Study:
- To investigate the interaction between XAF1 and FHL2.
- To elucidate the functional relationship between XAF1 and FHL2 in cancer cells.
- To understand the antagonistic mechanism between XAF1 and FHL2.
Main Methods:
- Yeast two-hybrid system to detect protein-protein interactions.
- Cellular localization studies in gastric cancer cells.
- Assessment of transcriptional activities of β-catenin and AP-1.
Main Results:
- FHL2 was identified as a binding protein for XAF1.
- Both XAF1 and FHL2 were found in the cytoplasm, mitochondria, and nucleus of gastric cancer cells.
- XAF1 overexpression excluded FHL2 from the nucleus and inhibited FHL2's stimulation of β-catenin and AP-1 transcriptional activities.
Conclusions:
- XAF1 and FHL2 interact and share cellular localization.
- XAF1 acts antagonistically to FHL2, suppressing its oncogenic functions.
- This study reveals a novel tumor suppressor mechanism involving XAF1 and FHL2 in cancer.
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