S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis

Yi, S.,Um, S.,Lee, J.,Yoo, J.,Bang, S.,Park, E.,Lee, M.,Nam, K.,Jeon, Y.,Park, J.,You, J.,Lee, S.J.,Bae, G.U.,Rhie, J.,Kozma, Sara C.,Thomas, G.,Han, J.W. Cell Press 2016 Molecular Cell Vol.62 No.3

S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

Development of a Saccharomyces cerevisiae strain for the production of 1,2-propanediol by gene manipulation

Jeon, E.,Lee, S.,Kim, D.,Yoon, H.,Oh, M.,Park, C.,Lee, J. IPC Science and Technology Press ; Elsevier Scienc 2009 Enzyme and microbial technology Vol.45 No.1

The main goal of this research was to achieve a more efficient production of 1,2-propanediol (1,2-PD) using mutated Saccharomyces cerevisiae. 1,2-PD cannot be produced by wild type S. cerevisiae. To develop a S. cerevisiae mutant that could produce 1,2-PD, the mgs gene of E. coli-K12 MG1655 and the dhaD gene of Citrobacter freundii were inserted into yeast expression vectors such as pESC-URA and pESC-TRP and transformed into the wild type of S. cerevisiae. As a result, the batch fermentation of S. cerevisiae YPH500, harboring an mgs gene inserted pJES27 vector, resulted in a yield of 0.17g/L. On the other hand, the methylglyoxal synthase of the recombinant S. cerevisiae YPH500, harboring a dhaD gene inserted pJES29 vector, was inactive and produced no detectable amount of 1,2-PD. Therefore, in order to achieve a maximum yield of 1,2-PD, we selected the pESC-TRP vector that is able to co-express the dhaD gene with the pJES27 vector. By inserting the dhaD gene into the pESC-TRP vector, the pJES30 vector was constructed. The maximal yield of 1,2-PD achieved in a 1% galactose batch fermentation by pJES27 and pJES30 harboring S. cerevisiae was 0.45g/L.

Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells

Jeon, T-Y,Han, M-E,Lee, Y-W,Lee, Y-S,Kim, G-H,Song, G-A,Hur, G-Y,Kim, J-Y,Kim, H-J,Yoon, S,Baek, S-Y,Kim, B-S,Kim, J-B,Oh, S-O Nature Publishing Group 2010 The British journal of cancer Vol.102 No.4

<P><B>Background:</B></P><P>Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described.</P><P><B>Methods:</B></P><P>Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA).</P><P><B>Results:</B></P><P>The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (<I>P</I>=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells <I>in vitro</I> were significantly inhibited. Moreover, s<I>tathmin1</I> siRNA transfection significantly slowed the growth of xenografts in nude mice.</P><P><B>Conclusion:</B></P><P>These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.</P>

Assignment of phosphatidylinositol glycan, class K (PIGK) gene to porcine chromosome 6q32 by somatic cell and radiation hybrid panel mapping

Park, E.W.,Kim, J.H.,Lim, H.T.,Seo, B.Y.,Cho, I.C.,Lee, J.G.,Oh, S.J.,Cheong, I.C.,Lee, J.H.,Jeon, J.T. S. Karger AG 2004 CYTOGENETIC AND GEN0ME RESEARCH Vol.108 No.4

<P> </P><P>Copyright © 2005 S. Karger AG, Basel</P>

Ribosomal protein S6 is a selective mediator of TRAIL-apoptotic signaling

Jeon, Y-J,Kim, I K,Hong, S-H,Nan, H,Kim, H-J,Lee, H-J,Masuda, E S,Meyuhas, O,Oh, B-H,Jung, Y-K Nature Publishing Group 2008 Oncogene Vol.27 No.31

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potent inducer of apoptosis in tumor cells and holds a promise as a therapeutic agent against cancer. To elucidate the death signaling evoked by TRAIL, we performed a functional genetic screening and rescued TRAIL-resistant Jurkat clones harboring ribosomal protein S6 (rpS6) cDNA in anti-sense frame. Reduction of rpS6 expression in Jurkat and HeLa cells attenuated apoptosis induced by TRAIL, but not those by other cell death signals, including tumor necrosis factor-α and cycloheximide, etoposide, doxorubicin, tunicamycin and staurosporine. Death receptor (DR) 4, but not DR5, was downregulated in rpS6 knockdown cells. Conversely, the sensitivity to TRAIL was increased by the ectopic expression of wild-type rpS6 and further by phospho-defective rpS6 mutant (S6-SS235,6AA), but not by phospho-mimic rpS6 mutant (S6-SS235,6DD). Also, unphosphorylatable rpS6 knock-in mouse embryo fibroblasts (rpS6<SUP>P−/−</SUP> MEFs) were more sensitive to TRAIL than control MEFs. In addition, SKHep-1 tumor cells, which express less phospho-rpS6 and are more sensitive to TRAIL than other tumor cells, became effectively desensitized to TRAIL after rpS6 knockdown. These results suggest that rpS6, especially in its unphosphorylated form, is a selective mediator of TRAIL-induced apoptosis.Oncogene (2008) 27, 4344–4352; doi:10.1038/onc.2008.73; published online 24 March 2008

ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

Jeon, B.N.,Yoon, J.H.,Han, D.,Kim, M.K.,Kim, Y.,Choi, S.H.,Song, J.,Kim, K.S.,Kim, K.,Hur, M.W. Elsevier Science 2017 Biochimica et biophysica acta. Gene regulatory mec Vol.1860 No.9

Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.

Assignment of the phosphoinositide-3-kinase, class 3 (PIK3C3) gene to porcine chromosome 6q22→q23 by somatic cell and radiation hybrid panel mapping

Kim, J.H.,Lee, Y.S.,Park, E.W.,Seo, B.Y.,Cho, I.C.,Lee, J.G.,Oh, S.J.,Lee, J.H.,Jeon, J.T. S. Karger AG 2004 CYTOGENETIC AND GEN0ME RESEARCH Vol.108 No.4

<P> </P><P>Copyright © 2005 S. Karger AG, Basel</P>

Satisfaction with mammography in the National Cancer Screening Programme participants of age 40s in Korea

JEON, B.Y.,LEE, H‐,Y.,PARK, E‐,C.,CHOI, K.S.,JUN, J.K.,KIM, Y.,HAN, M.A.,YOON, N‐,H.,KIM, E.J.,JEON, S.M. Blackwell Publishing Ltd 2011 European journal of cancer care Vol.20 No.6

<P>JEON B.Y., LEE H‐Y., PARK E‐C., CHOI K.S., JUN J.K., KIM Y., HAN M.A., YOON N‐H., KIM E.J. & JEON S.M. (2011) <I>European Journal of Cancer Care</I><B>20</B>, 803–809</P><P><B>Satisfaction with mammography in the National Cancer Screening Programme participants of age 40s in Korea</B></P><P>The aim of this study was to evaluate satisfaction with the National Cancer Screening Programme of mammography in Korea and to examine the association between subscales of satisfaction and general satisfaction. We conducted a cross‐sectional telephone survey for women who had obtained a National Cancer Screening Programme mammographic screening at general hospitals between May and October 2008. The present study included 2005 women in their forties. We performed multivariate linear regression using dependent variable as general satisfaction and independent variables as subscales of satisfaction, such as pre‐screening information transfer, staff interpersonal skills, physical surroundings and results reporting. Participants were stratified according to the result of their mammogram as negative or positive. Mean score of satisfaction was above 2.5 of 4 for all subscales. Women who received positive results were less satisfied with all of subscale factors. Staff interpersonal skills were the most important factor that contributed to general satisfaction. Future efforts such as staff training programme of communication/attitude skills, ensuring privacy and explanation of possible discomfort of the screening would be needed.</P>

Potential Effect of S-Nitrosylated Protein Disulfide Isomerase on Mutant SOD1 Aggregation and Neuronal Cell Death in Amyotrophic Lateral Sclerosis

Jeon, G. S.,Nakamura, T.,Lee, J. S.,Choi, W. J.,Ahn, S. W.,Lee, K. W.,Sung, J. J.,Lipton, S. A. HUMANA PRESS INC 2014 Molecular neurobiology Vol.49 No.2

Aggregation of misfolded protein and resultant intracellular inclusion body formation are common hallmarks of mutant superoxide dismutase (mSOD1)-linked familial amyotrophic lateral sclerosis (FALS) and have been associated with the selective neuronal death. Protein disulfide isomerase (PDI) represents a family of enzymatic chaperones that can fold nascent and aberrant proteins in the endoplasmic reticulum (ER) lumen. Recently, our group found that S-nitrosylated PDI could contribute to protein misfolding and subsequent neuronal cell death. However, the exact role of PDI in the pathogenesis of ALS remains unclear. In this study, we propose that PDI attenuates aggregation of mutant/misfolded SOD1 and resultant neurotoxicity associated with ER stress. ER stress resulting in PDI dysfunction therefore provides a mechanistic link between deficits in molecular chaperones, accumulation of misfolded proteins, and neuronal death in neurodegenerative diseases. In contrast, S-nitrosylation of PDI inhibits its activity, increases mSOD1 aggregation, and increases neuronal cell death. Specifically, our data show that S-nitrosylation abrogates PDI-mediated attenuation of neuronal cell death triggered by thapsigargin. Biotin switch assays demonstrate S-nitrosylated PDI both in the spinal cords of SOD1 (G93A) mice and human patients with sporadic ALS. Therefore, denitrosylation of PDI may have therapeutic implications. Taken together, our results suggest a novel strategy involving PDI as a therapy to prevent mSOD1 aggregation and neuronal degeneration. Moreover, the data demonstrate that inactivation of PDI by S-nitrosylation occurs in both mSOD1-linked and sporadic forms of ALS in humans as well as mice.

Identification of stathmin 1 expression induced by Epstein–Barr virus in human B lymphocytes

Baik, S. Y.,Yun, H. S.,Lee, H. J.,Lee, M. H.,Jung, S. E.,Kim, J. W.,Jeon, J. P.,Shin, Y. K.,Rhee, H. S.,Kimm, K. C.,Han, B. G. Blackwell Publishing Ltd 2007 Cell proliferation Vol.40 No.2

<P>Abstract. </P><P><I>Introduction</I>: The Epstein–Barr virus transforms resting B cells into proliferating lymphoblastoid cells, the origin of cell lines. <I>Method and results</I>: Our cDNA microarray analyses led to the identification of 232 up-regulated and 112 down-regulated genes with more than a 3-fold difference in lymphoblastoid cell lines compared to resting B cells. The functional classification of these genes exhibited the distinct expression signature for cell proliferation, cell cycle and an immune response. Among them, we verified the differential expression of several oncogenes such as <I>stathmin 1</I> (<I>STMN1</I>), <I>RAB27A</I>, <I>RAB9A</I>, <I>BACH1</I> and <I>BACH2</I> using quantitative real-time reverse transcriptase-polymerase chain reactions or Western blot analysis. Expression of <I>STMN1</I> (which is involved in regulation of the microtubule filament system, cell growth and S-phase of cell cycle) was increased in lymphoblastoid cell line as well as in 7-day post-Epstein–Barr virus infection B cells, compared to resting B cells. <I>Conclusion</I>: Thus, this study suggests that Epstein–Barr virus infection induces <I>STMN1</I> expression, which play a role in cell cycle progression and proliferation in the human B lymphocyte.</P>