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Akt/PKB interacts with the histone H3 methyltransferase SETDB1 and coordinates to silence gene expression

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Abstract

Serine/threonine kinase Akt (also called protein kinase B, PKB) is a downstream effector of phosphoinositide 3-kinase (PI3K) and functions as the focal point for many signal transduction pathways such as glucose metabolism, transcription, cell survival, angiogenesis, and cell motility. Akt is emerging as a central player in tumorigenesis including human ovarian, pancreatic, prostate, breast, and gastric cancers. However, the function and mechanism by which Akt regulate gene transcription in nucleus remains largely unclear. Here we identify histone methyltransferase SETDB1 as a novel nuclear interacting partner of Akt. By yeast two-hybrid screening, we obtained the Akt1-SETDB1 interaction and confirmed the binding both in vitro and in vivo. Both Akt1 and SETDB1 are co-localized in the nucleus in mammalian cells. SETDB1 is not a phosphorylation substrate of Akt kinase. Akt and SETDB1 could coordinate to regulate the activity of certain transcription factors such as forkhead family member. Due to the fact that SETDB1 acts as a specific histone H3, lysine 9-methyltransferase in vivo, we provide the first link between Akt kinase and histone methyltransferase (HMTase). This interaction represents a novel mechanism by which Akt regulates nuclear events including gene transcription.

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Acknowledgment

This work was supported by Chinese National Natural Science Foundation Projects (30600846).

Author information

Authors and Affiliations

  1. Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, 250012, PR China

    Haidong Gao, Liyu Jiang, Jingzhong Sun & Rong Ma

  2. Department of Breast Surgery, Second Affiliated of Shandong University, Jinan, 250012, PR China

    Zhigang Yu

  3. Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, PR China

    Dongsong Bi

  4. Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250012, PR China

    Yazhou Cui

  5. Department of Operation Research of Medicine School, Shandong University, Jinan, 250012, PR China

    Rong Ma

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  1. Haidong Gao
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  2. Zhigang Yu
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  3. Dongsong Bi
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  4. Liyu Jiang
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Correspondence to Rong Ma.

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Haidong Gao and Zhigang Yu contributed equally to this work.

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Gao, H., Yu, Z., Bi, D. et al. Akt/PKB interacts with the histone H3 methyltransferase SETDB1 and coordinates to silence gene expression. Mol Cell Biochem 305, 35–44 (2007). https://doi.org/10.1007/s11010-007-9525-3

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  • DOI: https://doi.org/10.1007/s11010-007-9525-3

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