DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells

Taira, Naoe; Mimoto, Rei; Kurata, Morito; Yamaguchi, Tomoko; Kitagawa, Masanobu; Miki, Yoshio; Yoshida, Kiyotsugu

doi:10.1172/jci60818

Cited by 114 publications

(165 citation statements)

References 53 publications

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“…In these regards, posttranscriptional regulation for the microRNA biogenesis is fundamental for tumor inhibition. We reported that DYRK2-depleted cells contribute to tumorigenesis in vivo (26,27). In the current study, AREG expression remained little, if any, detectable in the DYRK2 knockdown cells.…”

Section: Discussionmentioning

confidence: 99%

Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage

Taira

Yamaguchi

Kimura

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Upon DNA damage, tumor suppressor p53 determines cell fate by repairing DNA lesions to survive or by inducing apoptosis to eliminate damaged cells. The decision is based on its posttranslational modifications. Especially, p53 phosphorylation at Ser46 exerts apoptotic cell death. However, little is known about the precise mechanism of p53 phosphorylation on the induction of apoptosis. Here, we show that amphiregulin (AREG) is identified for a direct target of Ser46 phosphorylation via the comprehensive expression analyses. Ser46-phosphorylated p53 selectively binds to the promoter region of AREG gene, indicating that the p53 modification changes target genes by altering its binding affinity to the promoter. Although AREG belongs to a family of the epidermal growth factor, it also emerges in the nucleus under DNA damage. To clarify nuclear function of AREG, we analyze AREG-binding proteins by mass spectrometry. AREG interacts with DEAD-box RNA helicase p68 (DDX5). Intriguingly, AREG regulates precursor microRNA processing (i.e., miR-15a) with DDX5 to reduce the expression of antiapoptotic protein Bcl-2. These findings collectively support a mechanism in which the induction of AREG by Ser46-phosphorylated p53 is required for the microRNA biogenesis in the apoptotic response to DNA damage. microarray | Drosha | miRNA processing

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Section: Discussionmentioning

confidence: 99%

Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage

Taira

Yamaguchi

Kimura

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Finally, it was reported that TCE can cause hypomethylation of DNA and hyperexpression of oncogenes (e.g., MYC and JUG), responsible for uncontrolled cell proliferation [133][134][135][136][137] . A high prevalence of liver cancer was found in animal models exposed to PCE (CAS 127-18-4) [138,139] .…”

Section: -87-5mentioning

confidence: 99%

Hepatocellular carcinoma and the risk of occupational exposure

Rapisarda

Loreto

Malaguarnera

et al. 2016

WJH

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Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The main risk factors for HCC are alcoholism, hepatitis B virus, hepatitis C virus, nonalcoholic steatohepatitis, obesity, type 2 diabetes, cirrhosis, aflatoxin, hemochromatosis, Wilson's disease and hemophilia. Occupational exposure to chemicals is another risk factor for HCC. Often the relationship between occupational risk and HCC is unclear and the reports are fragmented and inconsistent. This review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem. Core tip: Hepatocellular carcinoma (HCC) is the fifth most common human cancer. This review summarizes current knowledge regarding the occupational risk factors of HCC. In particular, we underline not only the infective but also non-infective occupational risk exposure, including chemical agents and toxic metabolites which are a major cause of liver damage.

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“…Indeed, we found that DYRK2 phosphorylates c-Jun and c-Myc at Ser243 and Ser62, respectively. 8 In DYRK2 knockdown cells, subsequent phosphorylation of c-Jun and c-Myc by GSK3 is absent. Because mutations of these phosphorylation sites have been reported, regulation of c-Jun and c-Myc expression is critical for cancer development.…”

Section: Regulation Of G1/s Transition As a Priming Kinase For Gsk3mentioning

confidence: 99%

Engagement of DYRK2 in proper control for cell division

Nihira

Yoshida

2015

Cell Cycle

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Dysregulation of cell cycle machinery causes abnormal cell division, leading to cancer development. To drive cell cycle properly, expression levels of cell cycle regulators are tightly regulated through the cell cycle. Dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) is a Ser/Thr kinase, and its intracellular functions had not been elucidated for decades. Recent studies have shown that DYRK2 downregulates key molecules on cell cycle control. This review mainly highlights the DYRK2 function during cell division. In addition, we summarize tumor suppressive role of DYRK2 in cancer cells and discuss future research directions for DYRK2 toward the novel cancer therapies.

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DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells

Cited by 114 publications

References 53 publications

Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage

Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage

Hepatocellular carcinoma and the risk of occupational exposure

Engagement of DYRK2 in proper control for cell division

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