Rapid Downregulation of Cyclin D1 Induced by Geranylgeranoic Acid in Human Hepatoma Cells

Shimonishi, Shohei; Muraguchi, Takashi; Mitake, Maiko; Sakane, Chiharu; Okamoto, Kazushi; Shidoji, Yoshihiro

doi:10.1080/01635581.2012.655401

Cited by 9 publications

(13 citation statements)

References 46 publications

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“…Previous research has indicated that cyclin B1 is the main regulatory element of the cell cycle's G2 restriction point [14]. In addition, it is known that cyclin D1 is the main regulatory element of the G1/S phase [15]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

c‐MYB regulates cell growth and DNA damage repair through modulating MiR‐143

Wang¹,

Wu²,

Shi³

et al. 2015

FEBS Letters

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a b s t r a c tRadiotherapy is the most successful nonsurgical treatment for nasopharyngeal carcinoma (NCP). Although NPCs initially respond well to a full course of radiation, recurrence and metastasis are frequent. In this study, we found that down-regulated c-MYB expression was associated with increased radiation resistance and DNA damage repair ability. Interestingly, c-MYB was over-expressed in cancer tissues but not in the adjacent tissues. Down-regulation of c-MYB expression inhibited cell proliferation, and led to cell cycle arrest at the M phase in NPC cells. Luciferase and chromatin immunoprecipitation assays demonstrated that c-MYB transactivated miR-143 through direct binding to its promoter. Based on these results, c-MYB might target miR-143 in order to regulate stem cell properties, cell growth, apoptosis, and DNA damage repair.

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Section: Resultsmentioning

confidence: 99%

c‐MYB regulates cell growth and DNA damage repair through modulating MiR‐143

Wang¹,

Wu²,

Shi³

et al. 2015

FEBS Letters

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“…GGA has been repeatedly reported to induce cell death in HuH-7 cells181924. PUMA is a critical mediator of p53-dependent and -independent cell death4.…”

Section: Resultsmentioning

confidence: 99%

Induction of nuclear translocation of mutant cytoplasmic p53 by geranylgeranoic acid in a human hepatoma cell line

Iwao

Shidoji

2014

Sci Rep

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Mutant p53 proteins in human hepatoma cell lines such as HuH-7 (Y220C) and PLC/PRF/5 (R249S) accumulate in the cytoplasm, and lose their transcriptional function. Geranylgeranoic acid (GGA) is a naturally occurring acyclic diterpenoid that induces cell death in both cell lines, but not in HepG2 cells harboring wild-type p53. Here, we demonstrate that micromolar concentrations of GGA induce a rapid nuclear translocation of cytoplasmic p53 in both p53-mutant cell lines and p53 knockdown attenuates GGA-induced cell death in HuH-7 cells. Cell-free experiments demonstrate that GGA is able to release 670-kD p53-containing complexes from putative huge macromolecular aggregates in post-mitochondrial fractions as revealed on blue-native gradient PAGE. Among several p53-target genes tested, GGA upregulates PUMA gene expression, and ivermectin, an inhibitor for importin α/β, blocks GGA-induced nuclear translocation of cytoplasmic p53 and suppresses GGA-induced upregulation of PUMA mRNA levels in HuH-7 cells. Taken together, these data suggest that GGA treatment stimulates a nuclear translocation of mutant p53 through its dissociation from cytoplasmic aggregates, which may be essential for GGA-induced cell death.

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“…The earliest is cytoplasmic splicing of X-box binding protein 1 (XBP1) mRNA, a canonical marker for unfolded protein response (UPR), observed 5 min after adding GGA in culture medium (15). Overproduction of superoxide in mitochondria and conversion from LC3-I to LC3-II, a marker for initial autophagic response, can be detected after 15 min (16); and after 30 min, GFP-LC3 granules appear (16) and cyclin D1 protein disappears (17). Two hours after adding GGA, the XBP1s protein (derived from a spliced form of XBP1 mRNA) is detected in the nucleus (15), the cellular level of phosphorylated p53 at Ser10 is increased (18), and the membrane potential of mitochondria (m) is lost (16).…”

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confidence: 99%