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Annexin A4 interacts with the NF-κB p50 subunit and modulates NF-κB transcriptional activity in a Ca2+-dependent manner

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Abstract

Previously, we identified annexin A4 (ANXA4) as a candidate substrate of caspase-3. Proteomic studies were performed to identify interacting proteins with a view to determining the roles of ANXA4. ANXA4 was found to interact with the p105. Subsequent studies revealed that ANXA4 interacts with NF-κB through the Rel homology domain of p50. Furthermore, the interaction is markedly increased by elevated Ca2+ levels. NF-κB transcriptional activity assays demonstrated that ANXA4 suppresses NF-κB transcriptional activity in the resting state. Following treatment with TNF-α or PMA, ANXA4 also suppressed NF-κB transcriptional activity, which was upregulated significantly early after etoposide treatment. This difference may be due to the intracellular Ca2+ level. Additionally, ANXA4 translocates to the nucleus together with p50, and imparts greater resistance to apoptotic stimulation by etoposide. Our results collectively indicate that ANXA4 differentially modulates the NF-κB signaling pathway, depending on its interactions with p50 and the intracellular Ca2+ ion level.

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Acknowledgments

We would like to thank Professors Si Myung Byun, Young Min Kim, Yeon-Soo Seo, Jin Soo Kim and Brian S. Wilson for continuous encouragement and helpful advices. In addition, we thank Drs. Sunghyun Kang, Do Hee Lee, and Ah Young Lee for carefully reading the manuscript and providing insightful comments. This work was supported by a grant from the KRIBB (to K.-H. Bae), Korea Research Council of Fundamental Science and Technology (to K.-H. Bae) and of the Korea Science and Engineering Foundation (KOSEF) (to S. G. Park), the Korean Ministry of Education, Science and Technology.

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Authors and Affiliations

  1. Medical Proteomics Research Center, KRIBB, Daejeon, 305-806, Republic of Korea

    Young-Joo Jeon, Do-Hyung Kim, Hyeyun Jung, Sang J. Chung, Seung-Wook Chi, Sang Chul Lee, Byoung Chul Park, Sung Goo Park & Kwang-Hee Bae

  2. College of Pharmacy, Chung-Ang University, Seoul, 156-756, Republic of Korea

    Sayeon Cho

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  1. Young-Joo Jeon
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  2. Do-Hyung Kim
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  9. Sung Goo Park
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  10. Kwang-Hee Bae
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Correspondence to Sung Goo Park or Kwang-Hee Bae.

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Y.-J. Jeon and D.-H. Kim contributed equally to this work. K.-H. Bae and S. G. Park are co-last authors.

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Jeon, YJ., Kim, DH., Jung, H. et al. Annexin A4 interacts with the NF-κB p50 subunit and modulates NF-κB transcriptional activity in a Ca2+-dependent manner. Cell. Mol. Life Sci. 67, 2271–2281 (2010). https://doi.org/10.1007/s00018-010-0331-9

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