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Yoo, Jung-Yoon,Choi, Hyo-Kyoung,Choi, Kyung-Chul,Park, Soo-Yeon,Ota, Ichiro,Yook, Jong In,Lee, Yoo-Hyun,Kim, Kunhong,Yoon, Ho-Geun The American Society for Cell Biology 2012 Molecular biology of the cell Vol.23 No.15
<P>Aberrant expression of casein kinase 2 (CK2) is associated with tumor progression; however, the molecular mechanism by which CK2 modulates tumorigenesis is incompletely understood. In this paper, we show that CK2α phosphorylates the C-terminal domain of the nuclear receptor corepressor (NCoR) at Ser-2436 to stabilize the NCoR against the ubiquitin-dependent proteasomal degradation pathway. Importantly, NCoR promoted the invasion of esophageal cancer cells in a CK2-dependent manner. By using cyclic DNA microarray analysis, we identified CXCL10/IP-10 as a novel CK2α-NCoR cascade–regulated gene. The depletion of both NCoR and HDAC3 commonly derepressed IP-10 transcription, demonstrating the functional engagement of the NCoR-HDAC3 axis in IP-10 transcriptional repression. Furthermore, chromatin immunoprecipitation assays showed that c-Jun recruits NCoR-HDAC3 corepressor complexes to the (AP1 site of IP-10, leading to histone hypoacetylation and IP-10 down-regulation. Collectively these data suggest that the CK2α-NCoR cascade selectively represses the transcription of IP-10 and promotes oncogenic signaling in human esophageal cancer cells.</P>
( Kimio Ushijima ),( Shuji Takemoto ),( Kouichiro Kawano ),( Shin Nishio ),( Atsumu Terada ),( Naotake Tsuda ),( Gonosuke Sonoda ),( Syun Ichiro Ota ),( Toshiharu Kamura ) 대한산부인과학회 2012 Obstetrics & Gynecology Science Vol.55 No.4
Type III radical abdominal hysterectomy (RAH) is standard care for early stage cervical cancer. For the past few decades, there has been a remarkable shift from surgery to radiation, in the treatment choice for stage 1b2 and 2b cervical cancer in Japan. It is still controversial, however because some of those cases recommended RAH as a suitable treatment strategy. About 8% to 10% of RAH are abandoned because of tumor status. Recent preoperative screening cannot always detect them preoperatively. Various kinds of new surgical instruments, such as bipolar scissors and the electro vessel sealing system LigaSure have contributed to reducing the operation time and blood loss, in performing RAH. Furthermore, various kinds of devices are on the market. Surgeons should choose suitable instruments depending on the state of the disease and the patient.
Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells
Misa Nakamura,Takashi Ozaki,Aiko Ishii,Masayoshi Konishi,Yuji Tsubota,Toru Furui,Hayato Tsuda,Ichiro Mori,Kiichiro Ota,Kennichi Kakudo 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.5
Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney. Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.
Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition
Park, Sang Yoon,Kim, Hyun Sil,Kim, Nam Hee,Ji, Suena,Cha, So Young,Kang, Jeong Gu,Ota, Ichiro,Shimada, Keiji,Konishi, Noboru,Nam, Hyung Wook,Hong, Soon Won,Yang, Won Ho,Roth, Jü,rgen,Yook, Jong In Wiley (John WileySons) 2010 The EMBO journal Vol.29 No.22
Sang Yoon Park,Hyun Sil Kim,Nam Hee Kim,Suena Ji,So Young Cha,Jeong Gu Kang,Ichiro Ota,Keiji Shimada,Noboru Konishi,Hyung Wook Nam,Won Ho Yang,Jürgen Roth,Jong In Yook,Jin Won Cho 한국당과학회 2010 한국당과학회 학술대회 Vol.2010 No.1
Protein O-phosphorylation can occur reciprocal with O-GlcNAc modification and represents a regulatory principle for proteins. O-phosphorylation of serine by GSK-3β on Snail1, a transcriptional repressor of E-cadherin and a key regulator of the epithelial-mesenchymal transition (EMT) program, results in its proteasomal degradation. We show that Snail1 carries O-GlcNAc at serine112 that stabilizes it by suppressing O-phosphorylation-mediated degradation. Stabilization by O-GlcNAc of Snail1 results in attenuation of E-cadherin mRNA expression. Enhanced O-GlcNAc modification occurred under hyperglycemic conditions and initiated EMT by transcriptional suppression of E-cadherin through Snail1. Thus, a molecular link exists between cellular glucose metabolism and the control of EMT by dynamic reciprocal O-phosphorylation and O-GlcNAc modification of Snail1.
O-GlcNAc Modification on E-cadherin repressor Snail confers Epithelial-Mesenchymal Transition
Sang Yoon Park,Hyun Sil Kim,Nam Hee Kim,Won Ho Yang,Jeong Gu Kang,Suena Ji,Shi Eun Kang,Ichiro Ota,Keiji Shimada,Noboru Konishi,Mi Heon Ryu,Hyung Wook Nam,Jong In Yook,Jin Won Cho 한국당과학회 2009 한국당과학회 학술대회 Vol.2009 No.1
The transcriptional repressor Snail plays a key role in epithelial-mesenchymal transition (EMT) by which direct repression of E-cadherin transcription. Therefore, regulation of Snail expression level in epithelial tumor cells is important not only for maintaining of epithelial homeostasis, but also for invasion and metastasis of cancer cells by the EMT program. Series of Ser imbedded in Snail are phosphorylated by GSK3 and Snail expression is dynamically regulated by Wnt signaling together with β-catenin while driving a Snail-dependent EMT program. Glucose flux through the hexosamine biosynthetic pathway (HBP) can be used for the source of O-linked β-N-acetylglucosamine(O-GlcNAc) modification on Ser and Thr residues of various nucleocytoplasmic proteins. In this study, we demonstrate that Ser112 of Snail is O-GlcNAcylated and this adjacent-site occupancy inhibits phosphorylation by GSK-3, resulting in increased Snail stability and attenuation of E-cadherin proximal promoter activity and transcription level. Furthermore, Overexpression of OGT induces in vivo invasion program of epithelial cancer cells by Snail-dependent manner. Taken together, our results indicate dynamic interplay between O-GlcNAcylation and GSK-3 phosphorylation of Snail, and our observations may provide the molecular insight of pathogenic and prognostic correlation between cancer progression and hyperglycemic condition of diabetes.