http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Woo, Seon Rang,Lee, Hyo-Jung,Oh, Se Jin,Kim, Suyeon,Park, Sang-Hyo,Lee, Jaeyoon,Song, Kwon-Ho,Kim, Tae Woo Elsevier 2018 Biochemical and biophysical research communication Vol.503 No.3
<P><B>Abstract</B></P> <P>Cancer immunoediting enriches NANOG expression in tumor cells, resulting in multi-drug resistance and stem-like phenotypes. We previously demonstrated that these NANOG-associated phenotypes are promoted through HDAC1 transcriptional upregulation. In this study, we identified that NANOG also contributes to the stabilization of HDAC1 protein through the AKT signaling pathway. NANOG-AKT axis leads to phosphor-dependent inactivation of CHFR, an E3 ligase for HDAC1 protein, and thereby inhibiting the ubiquitin-mediated degradation of HDAC1. Furthermore, AKT inhibition disrupts HDAC1 WT-mediated phenotypes but had no effect on the phenotypes mediated by HDAC1 FM, a mutant that is unable to interact with CHFR. Critically, we applied a catalytic dead mutant, HDAC1-H141A, to uncover that HDAC1 confers immune-resistance, drug-resistance and stem-like phenotype in tumor cells through its catalytic activity. Collectively, our results establish a firm molecular link in immune-edited tumor cells among NANOG, AKT, CHFR, and HDAC1, identifying HDAC1 as a molecular target in controlling NANOGHIGH immune-refractory cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> NANOG contributes to stabilization of HDAC1 protein through AKT signaling pathway. </LI> <LI> NANOG-AKT axis leads to phosphor-dependent inactivation of CHFR, which is an E3 ligase for HDAC1 protein. </LI> <LI> HDAC1 confers immune-resistance, drug-resistance and stem-like phenotype through its catalytic activity. </LI> <LI> AKT inhibition disrupts HDAC1-mediated multi-resistance and stem-like phenotype. </LI> </UL> </P>
( Seon Rang Woo ),( Jeong Eun Park ),( Yang Hyun Kim ),( Yeun Jin Ju ),( Hyun Jin Shin ),( Hyun Yoo Joo ),( Eun Ran Park ),( Sung Hee Hong ),( Gil Hong Park ),( Kee Ho Lee ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.12
The synthetic machinery of ATF4 (activating transcription factor 4) is activated in response to various stress conditions involved in nutrient restriction, endoplasmic reticulum homeostasis, and oxidation. Stress-induced inhibition of proteasome activity triggers the unfolded protein response and endoplasmic reticulum stress, where ATF4 is crucial for consequent biological events. In the current study, we showed that the NAD+-dependent deacetylase, SIRT1, suppresses ATF4 synthesis during proteasome inhibition. SIRT1 depletion via transfection of specific siRNA into HeLa cells resulted in a significant increase in ATF4 protein, which was observed specifically in the presence of the proteasome inhibitor MG132. Consistent with SIRT1 depletion data, transient transfection of cells with SIRT1-overexpressing plasmid induced a decrease in the ATF4 protein level in the presence of MG132. Interestingly, however, ATF4 mRNA was not affected by SIRT1, even in the presence of MG132, indicating that SIRT1-induced suppression of ATF4 synthesis occurs under post-transcriptional control. Accordingly, we propose that SIRT1 serves as a negative regulator of ATF4 protein synthesis at the post-transcriptional level, which is observed during stress conditions, such as proteasome inhibition.
Woo, Seon Rang,Ham, Yunhee,Kang, Wonyoung,Yang, Heekyoung,Kim, Sujong,Jin, Juyoun,Joo, Kyeung Min,Nam, Do-Hyun Hindawi Publishing Corporation 2014 BioMed research international Vol.2014 No.-
<P>Standard treatment for glioblastoma comprises surgical resection, chemotherapy with temozolomide, and radiotherapy. Nevertheless, majority of glioblastoma patients have recurrence from resistance to the cytotoxic conventional therapies. We examined combinational effects of KML001, an arsenic compound targeting telomeres of chromosomes with temozolomide or irradiation, in glioblastoma cell lines and xenograft models, to overcome the therapeutic limitation of chemoradiation therapy for glioblastoma. Although KML001 alone showed little effects on <I>in vitro</I> survival of glioblastoma cells, cell death by <I>in vitro</I> temozolomide treatment or irradiation was synergistically potentiated by combination with KML001. Since phosphorylated <I>γ</I>-H2AX, cleaved casepase-3, and cleaved PARP were dramatically increased by KML001, the synergistic effects would be mediated by increased DNA damage and subsequent tumor cell apoptosis. Combinatorial effects of KML001 were observed not only in chemo- and radiosensitive glioblastoma cell line, U87MG, but also in the resistant cell line, U251MG. In the U87MG glioblastoma xenograft models, KML001 did not have systemic toxicity but showed synergistic therapeutic effects in combination with temozolomide or irradiation to reduce tumor volumes significantly. These data indicated that KML001 could be a candidate sensitizer to potentiate therapeutic effects of conventional cytotoxic treatment for glioblastoma.</P>