http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Lee, Jae-Jin,Park, Joon Kyu,Jeong, Jaeho,Jeon, Hyesung,Yoon, Jong-Bok,Kim, Eunice EunKyeong,Lee, Kong-Joo American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.10
<P>Fas-associated factor 1 (FAF1) is a ubiquitin receptor containing multiple ubiquitin-related domains including ubiquitin-associated (UBA), ubiquitin-like (UBL) 1, UBL2, and ubiquitin regulatory X (UBX). We previously showed that N-terminal UBA domain recognizes Lys<SUP>48</SUP>-ubiquitin linkage to recruit polyubiquitinated proteins and that a C-terminal UBX domain interacts with valosin-containing protein (VCP). This study shows that FAF1 interacts only with VCP complexed with Npl4-Ufd1 heterodimer, a requirement for the recruitment of polyubiquitinated proteins to UBA domain. Intriguingly, VCP association to C-terminal UBX domain regulates ubiquitin binding to N-terminal UBA domain without direct interaction between UBA and UBX domains. These interactions are well characterized by structural and biochemical analysis. VCP-Npl4-Ufd1 complex is known as the machinery required for endoplasmic reticulum-associated degradation. We demonstrate here that FAF1 binds to VCP-Npl4-Ufd1 complex via UBX domain and polyubiquitinated proteins via UBA domain to promote endoplasmic reticulum-associated degradation.</P>
Eunice Yoojin Lee,이대원,이경훈,임석아 대한암학회 2023 Cancer Research and Treatment Vol.55 No.4
Hormone receptor–positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2–positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.
Unique binding mode of Evogliptin with human dipeptidyl peptidase IV
Lee, Hyung Ki,Kim, Mi-Kyung,Kim, Ha Dong,Kim, Heung Jae,Kim, Ji Won,Lee, Jie-Oh,Kim, Chan-Wha,Kim, Eunice EunKyeong Elsevier 2017 Biochemical and biophysical research communication Vol. No.
<P><B>Abstract</B></P> <P>Evogliptin ((<I>R</I>)-4-((<I>R</I>)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(<I>tert-</I>butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (<I>S,R</I> diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S<SUB>1</SUB> pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S<SUB>2</SUB> extensive subsite, and that the multiple hydrogen bonds made by the (<I>R</I>)-β-amine group in the S<SUB>2</SUB> pocket and the contacts made by the (<I>R</I>)-<I>tert</I>-butyl group with Arg125 contribute to the high potency observed for Evogliptin.</P>
Crystal structure of the tRNA-specific adenosine deaminase from Streptococcus pyogenes
Lee, Won-Ho,Kim, Young Kwan,Nam, Ki Hyun,Priyadarshi, Amit,Lee, Eun Hye,Kim, Eunice Eunkyeong,Jeon, Young Ho,Cheong, Chaejoon,Hwang, Kwang Yeon Wiley Subscription Services, Inc., A Wiley Company 2007 Proteins Vol.68 No.4
Lee, Won-Kyu,Son, Sang Hyeon,Jin, Bong-Suk,Na, Jung-Hyun,Kim, Soo-Youl,Kim, Kook-Han,Kim, Eunice EunKyeong,Yu, Yeon Gyu,Lee, Hyung Ho National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.48
<P>Protein kinase CK2 is a ubiquitous kinase that can phosphorylate hundreds of cellular proteins and plays important roles in cell growth and development. Deregulation of CK2 is related to a variety of human cancers, and CK2 is regarded as a suppressor of apoptosis; therefore, it is a target of anticancer therapy. Nucleolar phosphoprotein 140 (Nopp140), which is an intrinsically disordered protein, interacts with CK2 and inhibits the latter’s catalytic activity in vitro. Interestingly, the catalytic activity of CK2 is recovered in the presence of <SMALL>d</SMALL>-<I>myo</I>-inositol 1,2,3,4,5,6-hexakisphosphate (IP<SUB>6</SUB>). IP<SUB>6</SUB> is widely distributed in animal cells, but the molecular mechanisms that govern its cellular functions in animal cells have not been completely elucidated. In this study, the crystal structure of CK2 in complex with IP<SUB>6</SUB> showed that the lysine-rich cluster of CK2 plays an important role in binding to IP<SUB>6</SUB>. The biochemical experiments revealed that a Nopp140 fragment (residues 568–596) and IP<SUB>6</SUB> competitively bind to the catalytic subunit of CK2 (CK2α), and phospho-Ser574 of Nopp140 significantly enhances its interaction with CK2α. Substitutions of K74E, K76E, and K77E in CK2α significantly reduced the interactions of CK2α with both IP<SUB>6</SUB> and the Nopp140-derived peptide. Our study gives an insight into the regulation of CK2. In particular, our work suggests that CK2 activity is inhibited by Nopp140 and reactivated by IP<SUB>6</SUB> by competitive binding at the substrate recognition site of CK2.</P>
Lee, Kyung Ho,Hwang, Jeong-Ah,Kim, Sun-Ok,Kim, Jung Hee,Shin, Sang Chul,Kim, Eunice EunKyeong,Lee, Kyung S.,Rhee, Kunsoo,Jeon, Byeong Hwa,Bang, Jeong Kyu,Cha-Molstad, Hyunjoo,Soung, Nak-Kyun,Jang, Jae American Society for Biochemistry and Molecular Bi 2018 The Journal of biological chemistry Vol.293 No.3
<P>Elevated expression of human enhancer filamentation 1 (HEF1; also known as NEDD9 or Cas-L) is an essential stimulus for the metastatic process of various solid tumors. This process requires HEF1 localization to focal adhesions (FAs). Although the association of HEF1 with FAs is considered to play a role in cancer cell migration, the mechanism targeting HEF1 to FAs remains unclear. Moreover, up-regulation of Polo-like kinase 1 (Plk1) positively correlates with human cancer metastasis, yet how Plk1 deregulation promotes metastasis remains elusive. Here, we report that casein kinase 1δ (CK1δ) phosphorylates HEF1 at Ser-780 and Thr-804 and that these phosphorylation events promote a physical interaction between Plk1 and HEF1. We found that this interaction is critical for HEF1 translocation to FAs and for inducing migration of HeLa cells. Plk1-docking phosphoepitopes were mapped/confirmed in HEF1 by various methods, including X-ray crystallography, and mutated for functional analysis in HeLa cells. In summary, our results reveal the role of a phosphorylation-dependent HEF1–Plk1 complex in HEF1 translocation to FAs to induce cell migration. Our findings provide critical mechanistic insights into the HEF1–Plk1 complex–dependent localization of HEF1 to FAs underlying the metastatic process and may therefore contribute to the development of new cancer therapies.</P>
Lee, Choongman,Park, Joon Kyu,Youn, Yeoan,Kim, Joo Hyoung,Lee, Kyo-Seok,Kim, Nak-kyoon,Kim, Eunji,Kim, Eunice Eunkyeong,Yoo, Kyung-Hwa American Chemical Society 2017 ANALYTICAL CHEMISTRY - Vol.89 No.4
<P>We employed modified glass nanocapillaries to investigate interactions between the RNA-binding protein, known as cell carcinoma antigen recognized by T cells-3 (SART3), and the noncoding spliceosome component, U6 small nuclear RNA (snRNA), at the single-molecule level. We functionalized the nanocapillaries with U6 snRNA fragments, which were hybridized to DNA molecules and then covalently attached to the nanocapillary surface. When transported through the modified nanocapillaries, two different SART3-derived constructs, HAT-RRM1-RRM2 and RRM1-RRM2, exhibited resistive ionic current pulses with different dwell times, which represented their different binding affinities to tethered U6 snRNAs. The dissociation constants (K-D), estimated from the bias voltage dependence of translocation events, were approximately 1.9 mu M and 201 mu M for HAT-RRM1-RRM2 and RRM1-RRM2, respectively. These values were comparable to corresponding values obtained with isothermal titration calorimetry, demonstrating that the modified glass nanocapillaries are applicable to analyses of protein ligand interactions at the single-molecule level.</P>