The Nucleolar Protein Myb-binding Protein 1A (MYBBP1A) Enhances p53 Tetramerization and Acetylation in Response to Nucleolar Disruption

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

doi:10.1074/jbc.m113.474049

Cited by 32 publications

(27 citation statements)

References 79 publications

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“…We pulled down RNA-protein complexes using streptavidin beads and identified PURPL -associated proteins by mass spectrometry (Table S3). MYBBP1A, a protein known to stabilize p53, was strongly enriched (Figures 5A–C) in the PURPL pulldowns (Ono et al, 2014, Kuroda et al, 2011, Kumazawa et al, 2015, Akaogi et al, 2013). MYBBP1A is a predominantly nucleolar protein that associates with RNA and directly binds to p53 in the nucleoplasm resulting in p53 activation and stabilization (Ono et al, 2014, Kuroda et al, 2011, Hochstatter et al, 2012, George et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…We show that loss of PURPL results in elevated basal p53 levels and impaired cell growth in vitro and in vivo . PURPL regulates basal p53 levels by associating with MYBBP1A, a protein known to bind to and activate p53 (Ono et al, 2014, Kuroda et al, 2011, Kumazawa et al, 2015). Altogether, our study provides functional insights on PURPL , demonstrating a role of this lncRNA in suppressing basal p53 levels.…”

Section: Introductionmentioning

confidence: 99%

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Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer

et al. 2017

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SUMMARY Basal p53 levels are tightly suppressed under normal conditions. Disrupting this regulation results in elevated p53 levels to induce cell cycle arrest, apoptosis and tumor suppression. Here, we report the suppression of basal p53 levels by a nuclear, p53-regulated long noncoding RNA that we termed PURPL (p53 upregulated regulator of p53 levels). Targeted depletion of PURPL in colorectal cancer cells results in elevated basal p53 levels and induces growth defects in cell culture and in mouse xenografts. PURPL associates with MYBBP1A, a protein that binds to and stabilizes p53, and inhibits the formation of the p53-MYBBP1A complex. In the absence of PURPL, MYBBP1A interacts with and stabilizes p53. Silencing MYBBP1A significantly rescues basal p53 levels and proliferation in PURPL-deficient cells, suggesting that MYBBP1A mediates the effect of PURPL in regulating p53. These results reveal a p53-PURPL autoregulatory feedback loop and demonstrate a role for PURPL in maintaining basal p53 levels.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer

et al. 2017

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“…It has also been found that MYBBP1A plays an important role in the acetylation and activation of p53 [2,[28][29][30][31][32]. Under stress conditions in the nucleolus, which are produced by the inhibition of the ribosome synthesis or by the absence of glucose, rRNA transcription is blocked, and the RNA content in the nucleolus is reduced.…”

Section: Mybbp1a and Epigenetic Regulationmentioning

confidence: 99%

“…Both MYBBP1A-p53 binding sites (aa 643-1150 and aa 1151-1328) are required to facilitate p53 tetramerization and acetylation, so that only full-length MYBBP1A is able to promote p53 activation. Finally, the tetramer of acetylated p53, still bound to p300, binds to the promoters of its target genes and induces the expression of genes related to apoptosis and/or cell cycle arrest [31].…”

Section: Mybbp1a and Epigenetic Regulationmentioning

confidence: 99%

The Tumor Suppressor Roles of MYBBP1A, a Major Contributor to Metabolism Plasticity and Stemness

Felipe‐Abrio

Carnero

2020

Cancers

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The MYB binding protein 1A (MYBBP1A, also known as p160) acts as a co-repressor of multiple transcription factors involved in many physiological processes. Therefore, MYBBP1A acts as a tumor suppressor in multiple aspects related to cell physiology, most of them very relevant for tumorigenesis. We explored the different roles of MYBBP1A in different aspects of cancer, such as mitosis, cellular senescence, epigenetic regulation, cell cycle, metabolism plasticity and stemness. We especially reviewed the relationships between MYBBP1A, the inhibitory role it plays by binding and inactivating c-MYB and its regulation of PGC-1α, leading to an increase in the stemness and the tumor stem cell population. In addition, MYBBP1A causes the activation of PGC-1α directly and indirectly through c-MYB, inducing the metabolic change from glycolysis to oxidative phosphorylation (OXPHOS). Therefore, the combination of these two effects caused by the decreased expression of MYBBP1A provides a selective advantage to tumor cells. Interestingly, this only occurs in cells lacking pVHL. Finally, the loss of MYBBP1A occurs in 8%–9% of renal tumors. tumors, and this subpopulation could be studied as a possible target of therapies using inhibitors of mitochondrial respiration.

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“…The nucleolar protein Myb-binding protein 1α (MYBBP1A) is known for enhancing p53 tetramerization by directly interacting with p53 [11]. Recently, MYBBP1A was identified as a binding partner of PARIS (parkin-interacting substrate, ZNF746), which suppresses rRNA transcription and increased p53, a molecular marker of nucleolar stress, in the SN of conditional parkin KO mice and in sporadic PD patients [12].…”

Section: Introductionmentioning

confidence: 99%

Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients

Lee

Park³

et al. 2019

JCM

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The inactivation of parkin by mutation or post-translational modification contributes to dopaminergic neuronal death in Parkinson’s disease (PD). The substrates of parkin, FBP1 and AIMP2, are accumulated in the postmortem brains of PD patients, and it was recently suggested that these parkin substrates transcriptionally activate deubiquitinase USP29. Herein, we newly identified 160 kDa myb-binding protein (MYBBP1A) as a novel substrate of USP29. Knockdown of parkin increased the level of AIMP2, leading to ultimately USP29 and MYBBP1A accumulation in SH-SY5Y cells. Notably, MYBBP1A was downregulated in the ventral midbrain (VM) of Aimp2 knockdown mice, whereas the upregulation of MYBBP1A was observed in the VM of inducible AIMP2 transgenic mice, as well as in the substantia nigra of sporadic PD patients. These results suggest that AIMP2 upregulates USP29 and MYBBP1A in the absence of parkin activity, contributing to PD pathogenesis.

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The Nucleolar Protein Myb-binding Protein 1A (MYBBP1A) Enhances p53 Tetramerization and Acetylation in Response to Nucleolar Disruption

Cited by 32 publications

References 79 publications

Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer

Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer

The Tumor Suppressor Roles of MYBBP1A, a Major Contributor to Metabolism Plasticity and Stemness

Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients

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