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RBB, a novel transcription repressor, represses the transcription of HDM2 oncogene

Oncogene volume 32, pages 3711–3721 (2013)Cite this article

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Abstract

The p53 tumor suppressor is important in many aspects of cell biology. Tight regulation of p53 is thus imperative for maintaining cell homeostasis and preventing tumorigenesis. The stabilization and activity of p53 is primarily regulated by MDM2, which is encoded for by HDM2. However, how the expression and activity of MDM2 is regulated remains largely unknown. Here, we report a novel BTB and BEN domains-containing protein, RBB. We demonstrated that RBB is a novel transcriptional repressor binding specific DNA motif via a homodimer and interacting with the nucleosome remodeling and deacetylase (NuRD) complex. Genome wide transcription target analysis by ChIP sequencing revealed that RBB represses the transcription of a series of functionally important genes including HDM2. We showed that RBB recruits the NuRD complex to the internal promoter of HDM2 and inhibits the expression of MDM2 protein, leading to subsequent stabilization of tumor suppressor p53. Significantly, we showed that RBB suppresses cell proliferation and sensitizes cells to DNA damage-induced apoptosis. Our data indicate that RBB is a novel transcriptional repressor and an important regulator of p53 pathway.

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Acknowledgements

This work was supported by grants (81000876, 81130048 and 30921062 to YS) from the National Natural Science Foundation of China and grants (973 Program: 2011CB504204 to YS) from the Ministry of Science and Technology of China.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China

    C Xuan, Q Wang, Y Duan, L Li, L Shi, Y Wang, L Shan, Z Yao & Y Shang

  2. Department of Immunology, Tianjin Medical University, Tianjin, China

    Q Wang & Z Yao

  3. Department of Biochemistry and Molecular Biology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Health Science Center, Beijing, China

    X Han

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  1. C Xuan
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Xuan, C., Wang, Q., Han, X. et al. RBB, a novel transcription repressor, represses the transcription of HDM2 oncogene. Oncogene 32, 3711–3721 (2013). https://doi.org/10.1038/onc.2012.386

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