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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.
화학적 , 대사적 산화반응중 생성되는 S - oxide 를 이용한 O - ethyl S - methyl ethylphosphonothioate (1) 의 독성 기작에 관한 연구
허장현,한대성 ( J . H . Hur,T . R . Fukuto,D . S . Han ) 한국환경농학회 1991 한국환경농학회지 Vol.10 No.2
O-ethyl S-methyl ethylphosphonothioate [LD_(50) (rat, oral) 4.6㎎/㎏ : K_i(bovine erythrocyte acetylcholinesterase) 303 M^(-1min-1)] was selected as a model compound to study the mode of action of O, S-dialkyl alkylphosphonothioates which have been hypothesized to be toxic via a bioactivation process. Two chemical oxidants, meta-chloroperoxybenzoic acid and monoperoxyphthalic acid, and rat liver microsomal oxidases were used to mimic the action of mixed function oxidases on the model compound. The formation of S-oxide, a very unstable active intermediate, was proposed based on the identification of metabolic products. Furthermore, a trapping experiment with ethanol showed that the unstable intermediate S-oxide had the ability to phosphorylate acetylcholinesterase which is an important enzyme in nerve systems. The S-oxide intermediates are presumed to be responsible for the toxicity of O,S-dialkyl alkylphosphonothioates.
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>
GC/FPD를 이용한 현미, 대두, 고추, 감귤 중 Pyraclofos의 개별 분석법 확립
김지윤 ( J Y Kim ),김자영 ( J Y Kim ),김경진 ( K J Kim ),김다솜 ( D S Kim ),김해나 ( H N Kim ),허장현 ( J H Hur ) 강원대학교 농업생명과학연구원(구 농업과학연구소) 2013 강원 농업생명환경연구 Vol.25 No.3
In the present study, a single residual analytical method was developed for pyraclofos. Pyraclofos was analyzed in brown rice, soyabean, green pepper, and mandarin. For pyraclofos, samples were extracted with acetonitrile, concentrated and partitioned with dichloromethane and analyzed with GC/FPD. The limit of quantitation (LOQ) for fosthiazate was 0.1 ng (S/N>10) and method limit of quantitation (MLOQ) was 0.02 mg/kg. Recovery ranged through 78.1%-117.7% at fortification level of 0.02 (MLOQ), 0.2 (10×MLOQ), and 1.0 (50×MLOQ). The coefficient of variation (CV) for both the pesticides was less than 10% regardless of sample types. These results were further confirmed with GC/MS, respectively.
농산물 중 살충제,살선충제 Fosthiazate의 개별 잔류분석법 확립
김지윤 ( J Y Kim ),김자영 ( J Y Kim ),김경진 ( K J Kim ),김다솜 ( D S Kim ),김해나 ( H N Kim ),허장현 ( J H Hur ) 강원대학교 농업생명과학연구원(구 농업과학연구소) 2013 강원 농업생명환경연구 Vol.25 No.2
In the present study, a single residual analytical method was developed for fosthiazate. Fosthiazate was analyzed in brown rice, soybean, green pepper, and mandarin. For fosthiazate, samples were extracted with acetonitrile, concentrated and partitioned with dichloromethane and analyzed with GC/FPD. The limit of quantitation (LOQ) for fosthiazate was 0.1 ng (S/N>10) and method limit of quantitation (MLOQ) was 0.02 mg/kg. Recovery ranged through 80.7-111.3% at fortification level of 0.02 (MLOQ), 0.2 (10×MLOQ), and 1.0 (50×MLOQ). The coefficient of variation (CV) for both the pesticides was less than 10% regardless of sample types. These results were further confirmed with GC/MS, respectively.
에어컨 실내기의 공력소음 예측을 위한 RANS 난류모델의 성능 평가
민윤홍(Y.H. Min),강성원(S. Kang),허남건(N. Hur),이창훈(C. Lee),박정택(J. Park) 한국전산유체공학회 2012 한국전산유체공학회지 Vol.17 No.4
The objective of the present study is to investigate the effects of various turbulence models on the aerodynamic noise of an air-conditioner (AC) indoor unit. The results from URANS (unsteady Reynolds-averaged Navier-Stokes) simulations with the standard k-ε, k-ω shear stress transport (SST) and Spalart-Allmaras (S-A) turbulence models were analyzed and compared with the noise data from the experiments. The frequency spectra of the far-field acoustic pressure were computed using the Farrasat equation derived from the Ffowcs Williams-Hawkings (FW-H) equation based on the acoustic analogy model. Two fixed fan casings and the rotating cross-flow fan were used as the source surfaces of the dipole noise in the Farrasat equation. The result with the standard k-ε model showed a much better agreement with the experimental data compared to the k-w SST and S-A models. The differences in the pressure spectra from the different turbulence models were discussed based on the instantaneous vorticity fields. It was found that the over-estimated power spectra with the k-w SST and S-A models are related to the emphasized small-scale vortices produced with these models.