Nucleolar protein, Myb-binding protein 1A, specifically binds to nonacetylated p53 and efficiently promotes transcriptional activation

Ono, Wakana; Akaogi, Kensuke; Waku, Tsuyoshi; Kuroda, Takeshi; Yokoyama, Wataru; Hayashi, Yoshihiko; Kimura, Kazuhiro; Kishimoto, Hiroyuki; Yanagisawa, Junn

doi:10.1016/j.bbrc.2013.04.006

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…Finally, p53 transcriptional activity is mediated by acetylation by its coactivator p300/CBP; this is facilitated by neddylated RPL11 and MYBBP1A, which is sequestered in the nucleolus and released upon nucleolar stress [160], [161], [151] and [162].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Targeting the nucleolus for cancer intervention

Quin

Devlin

Cameron

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

207

235

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The contribution of the nucleolus to cancer is well established with respect to its traditional role in facilitating ribosome biogenesis and proliferative capacity. More contemporary studies however, infer that nucleoli contribute a much broader role in malignant transformation. Specifically, extra-ribosomal functions of the nucleolus position it as a central integrator of cellular proliferation and stress signaling, and are emerging as important mechanisms for modulating how oncogenes and tumor suppressors operate in normal and malignant cells. The dependence of certain tumor cells to co-opt nucleolar processes to maintain their cancer phenotypes has now clearly been demonstrated by the application of small molecule inhibitors of RNA Polymerase I to block ribosomal DNA transcription and disrupt nucleolar function (Bywater et al., 2012 [1]). These drugs, which selectively kill tumor cells in vivo while sparing normal cells, have now progressed to clinical trials. It is likely that we have only just begun to scratch the surface of the potential of the nucleolus as a new target for cancer therapy, with "suppression of nucleolar stress" representing an emerging "hallmark" of cancer. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Targeting the nucleolus for cancer intervention

Quin

Devlin

Cameron

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

207

235

View full text Add to dashboard Cite

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“…Nucleolar localisation of MYBBP1A depends on nucleolar RNA content. Inhibited rRNA transcription following DNA damage or glucose starvation leads to reduced nucleolar RNA content and translocation of MYBBP1A from the nucleolus to the nucleoplasm, where it binds nonacetylated p53, facilitates the interaction between p53 and histone acetyltransferase p300 and induces p53 acetylation and tetramerisation 47 48 49 50 . Then, MYBBP1A dissociates from the acetylated form of p53.…”

mentioning

confidence: 99%

Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A

Kumazawa

Nishimura

Katagiri

et al. 2015

Sci Rep

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The nucleolus, whose primary function is ribosome biogenesis, plays an essential role in p53 activation. Ribosome biogenesis is inhibited in response to cellular stress and several nucleolar proteins translocate from the nucleolus to the nucleoplasm, where they activate p53. In this study, we analysed precisely how impaired ribosome biogenesis regulates the activation of p53 by depleting nucleolar factors involved in rRNA transcription or rRNA processing. Nucleolar RNA content decreased when rRNA transcription was inhibited. In parallel with the reduced levels of nucleolar RNA content, the nucleolar protein Myb-binding protein 1 A (MYBBP1A) translocated to the nucleoplasm and increased p53 acetylation. The acetylated p53 enhanced p21 and BAX expression and induced apoptosis. In contrast, when rRNA processing was inhibited, MYBBP1A remained in the nucleolus and nonacetylated p53 accumulated, causing cell cycle arrest at the G1 phase by inducing p21 but not BAX. We propose that the nucleolus functions as a stress sensor to modulate p53 protein levels and its acetylation status, determining cell fate between cell cycle arrest and apoptosis by regulating MYBBP1A translocation.

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“…MYBBP1A is a nucleolar protein that has been reported to bind to transcription factors and regulate their activity [ 26 , 27 ]. It has been reported that MYBBP1A is able to stabilize the p53 protein and promote p53 activity by directly binding to p53, facilitating the p53-p300 interaction and thus enhancing p53 acetylation [ 28 , 29 ]. Consistent with previous studies, our results supported that MYBBP1A could stabilize p53 protein by using CHX (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…MYBBP1A was first identified for its binding to the negative regulatory domain of MYB [ 27 ]. Studies have shown that MYBBP1A can bind to p53 and enhance p53 acetylation, therefore influencing the stability and activity of p53 [ 28 , 29 , 51 ]. LncRNAs may play a role in the regulation of the function of MYBBP1A via direct interaction.…”

Section: Discussionmentioning

confidence: 99%

NAT10-mediated upregulation of GAS5 facilitates immune cell infiltration in non-small cell lung cancer via the MYBBP1A-p53/IRF1/type I interferon signaling axis

Wang,

Luo,

Huang

et al. 2024

Cell Death Discov.

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Interactions of tumor cells with immune cells in the tumor microenvironment play an important role during malignancy progression. We previously identified that GAS5 inhibited tumor development by suppressing proliferation of tumor cells in non-small cell lung cancer (NSCLC). Herein, we discovered a tumor-suppressing role for tumor cell-derived GAS5 in regulating tumor microenvironment. GAS5 positively coordinated with the infiltration of macrophages and T cells in NSCLC clinically, and overexpression of GAS5 promoted macrophages and T cells recruitment both in vitro and in vivo. Mechanistically, GAS5 stabilized p53 by directly binding to MYBBP1A and facilitating MYBBP1A-p53 interaction, and enhanced p53-mediated transcription of IRF1, which activated type I interferon signaling and increased the production of downstream CXCL10 and CCL5. We also found that activation of type I interferon signaling was associated with better immunotherapy efficacy in NSCLC. Furthermore, the stability of GAS5 was regulated by NAT10, the key enzyme responsible for N4-acetylcytidine (ac4C) modification, which bound to GAS5 and mediated its ac4C modification. Collectively, tumor cell-derived GAS5 could activate type I interferon signaling via the MYBBP1A-p53/IRF1 axis, promoting immune cell infiltration and potentially correlating with immunotherapy efficacy, which suppressed NSCLC progression. Our results suggested GAS5 as a promising predictive marker and potential therapeutic target for combination therapy in NSCLC.

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Nucleolar protein, Myb-binding protein 1A, specifically binds to nonacetylated p53 and efficiently promotes transcriptional activation

Cited by 5 publications

References 29 publications

Targeting the nucleolus for cancer intervention

Targeting the nucleolus for cancer intervention

Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A

NAT10-mediated upregulation of GAS5 facilitates immune cell infiltration in non-small cell lung cancer via the MYBBP1A-p53/IRF1/type I interferon signaling axis

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