CACUL1/CAC1 attenuates p53 activity through PML post-translational modification

Fukuda, Tomomi; Kigoshi-Tansho, Yu; Naganuma, Takao; Kazaana, Akira; Okajima, Tomomi; Tsuruta, Fuminori; Chiba, Tomoki

doi:10.1016/j.bbrc.2016.11.125

Cited by 11 publications

(10 citation statements)

References 25 publications

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“…Previous studies have shown that abnormal cell cycle regulation promotes the development of Alzheimer's disease and leads to apoptosis by regulating p53 protein activation. Moreover, downregulation of CACUL1 levels activates the p53 signaling pathway (Kong et al ; Fukuda et al ). The activation of the p53 protein, which is an important regulator of apoptosis, has been shown to be involved in promoting the expression of pro‐apoptotic members of the BCL‐2 family (Fukuda et al ; Sharma et al ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, downregulation of CACUL1 levels activates the p53 signaling pathway (Kong et al ; Fukuda et al ). The activation of the p53 protein, which is an important regulator of apoptosis, has been shown to be involved in promoting the expression of pro‐apoptotic members of the BCL‐2 family (Fukuda et al ; Sharma et al ). Taken together, the published studies suggest that downregulated CCNA2 and CACUL1 may be involved in cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Yan

et al. 2019

Journal of Neurochemistry

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Circulating microRNAs (miRNAs) have emerged as diagnostic and prognostic biomarkers for traumatic brain injury (TBI). However, a comprehensive characterization of the serum miRNA profile in patients with TBI and the roles of these potential markers in neuronal regulation have rarely been reported. In this study, the levels of 754 serum miRNAs were initially determined in two pooled samples of 15 severe traumatic brain injury (sTBI) patients and 15 healthy controls using a TaqMan Low Density Array. The markedly upregulated miRNAs in sTBI patients were subsequently validated individually by quantitative reverse-transcription PCR (RT-qPCR) in another larger cohort consisting of 81 sTBI patients, 81 mild traumatic brain injury (mTBI) patients and 82 age/sex-matched healthy controls. Seven miRNAs, including miR-103a-3p, miR-219a-5p, miR-302d-3p, miR-422a, miR-518f-3p, miR-520d-3p and miR-627, were significantly upregulated in both sTBI and mTBI patients compared with their expression in controls. Among these miRNAs, miR-219a-5p not only discriminated sTBI and mTBI patients from controls but also discriminated between sTBI and mTBI patients. We further show here that in the neuronal cell injury model, upregulated miR-219a-5p inhibits the expression of CCNA2 and CACUL1 and further regulates akt/Foxo3a and p53/Bcl-2 signaling pathways, causing a notable change in the expression of cleaved caspase-3, thereby inducing neuronal apoptosis. These results indicate that these seven selected miRNAs could serve as novel biomarkers for TBI. In particular, miR-219a-5p is a potentially valuable indicator of the diagnosis, prognosis of TBI and appears to regulate neuronal apoptosis and death. Keywords: biomarker, CACUL1, CCNA2, microRNA, miR-219a-5p, traumatic brain injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Yan

et al. 2019

Journal of Neurochemistry

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“…The role of the SIM in PML-IV is probably not limited to mediating interactions with SUMO, but more importantly, it regulates the functions of the 8b region. PML-IV is the only isoform that can activate p53 and induce cellular senescence upon over-expression, and thus it has been extensively studied (Peche et al, 2012;Ivanschitz et al, 2015;Fukuda et al, 2017). A recent study reported that the 8b region could interact with ARF and promote global SUMOylation, particularly that of p53 (Ivanschitz et al, 2015).…”

Section: Sim (mentioning

confidence: 99%

C-terminal motifs in promyelocytic leukemia protein isoforms critically regulate PML nuclear body formation

Peng

Wan

et al. 2017

Journal of Cell Science

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Promyelocytic leukemia protein (PML) nuclear bodies (NBs), which are sub-nuclear protein structures, are involved in a variety of important cellular functions. PML-NBs are assembled by PML isoforms, and contact between small ubiquitin-like modifiers (SUMOs) with the SUMO interaction motif (SIM) are critically involved in this process. PML isoforms contain a common N-terminal region and a variable C-terminus. However, the contribution of the C-terminal regions to PML-NB formation remains poorly defined. Here, using high-resolution microscopy, we show that mutation of the SIM distinctively influences the structure of NBs formed by each individual PML isoform, with that of PML-III and PML-V minimally changed, and PML-I and PML-IV dramatically impaired. We further identify several C-terminal elements that are important in regulating NB structure and provide strong evidence to suggest that the 8b element in PML-IV possesses a strong ability to interact with SUMO-1 and SUMO-2, and critically participates in NB formation. Our findings highlight the importance of PML C-termini in NB assembly and function, and provide molecular insight into the PML-NB assembly of each distinctive isoform.

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“…How other candidates contributes to senescence will be our future interest. Cacul1 was found to down-regulate p53 transcriptional activity, regulation oxidative pressure and apoptosis (Kong et al, 2013;Kigoshi et al, 2015;Fukuda et al, 2017), which suggest Cacul1 may act as a suppress factor in cell aging process. Trdmt1 plays an important role in tRNA methylation to prevent tRNA cleavage into fragment, thus stabilize overall translation (Ghanbarian et al, 2016;Jeltsch et al, 2017).…”

Section: Discussionmentioning

confidence: 97%

mTORC1-Rps15 Axis Contributes to the Mechanisms Underlying Global Translation Reduction During Senescence of Mouse Embryonic Fibroblasts

et al. 2019

Front. Cell Dev. Biol.

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The reduction of protein translation is a common feature in senescent cells and aging organisms, yet the underlying mechanisms are not fully understood. Here we show that both global mRNA translation and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) kinase activity are declined in a senescent model of mouse embryonic fibroblasts (MEFs). Furthermore, RNA-seq analyses from polysomal versus total mRNA fractions identify TOP-like mRNA of Rps15 whose translation is regulated by mTORC1 during MEF senescence. Overexpression of Rps15 delays MEF senescence, possibly through regulating ribosome maturation. Together, these findings indicate that the activation of mTORC1-Rps15 axis ameliorate senescence by regulating ribosome biogenesis, which may provide further insights into aging research.

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CACUL1/CAC1 attenuates p53 activity through PML post-translational modification

Cited by 11 publications

References 25 publications

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

C-terminal motifs in promyelocytic leukemia protein isoforms critically regulate PML nuclear body formation

mTORC1-Rps15 Axis Contributes to the Mechanisms Underlying Global Translation Reduction During Senescence of Mouse Embryonic Fibroblasts

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