NEDD4L limits cAMP signaling through ubiquitination of CREB‐regulated transcription coactivator 3

Kim, Yo‐,Han,Yoo, Hanju,Hong, A‐,Reum,Kwon, Minseo,Kang, Sang‐,Wook,Kim, Kyunggon,Song, Youngsup Federation of American Society for Experimental Bi 2018 The FASEB Journal Vol.32 No.7

<P>The transcription factor cAMP-responsive element-binding protein (CREB) is involved in a variety of physiologic processes. Although its activity appears to be largely correlated with its phosphorylation status, cAMP-mediated dephosphorylation and the subsequent nuclear migration of the CREB-regulated transcription factors (CRTCs) are required to stimulate CREB transcriptional activity. Among the 3 identified mammalian homologs of CRTCs, CRTC3 has been shown to be expressed predominantly in adipose tissues in response to catecholamine signals that regulate lipid metabolism. Here, we show that prolonged cAMP signaling down-regulates CRTC3 in a proteasome-dependent manner and that neural precursor cell-expressed developmentally down-regulated gene 4-like (NEDD4L), a specific ubiquitin ligase for CRTC3, is responsible for this process. By recognizing the PY motif of CRTC3, NEDD4L interacts with CRTC3 and promotes its polyubiquitination. Interaction between NEDD4L and CRTC3 is further boosted by cAMP signaling, and this enhanced interaction appears to be dependent on the cAMP-mediated phosphorylation of NEDD4L at the Ser448 site. Furthermore, we show that food withdrawal stimulates NEDD4L phosphorylation in mice, which then show a decrease of adipose tissue CRTC3 protein levels. Together, these results suggest that NEDD4L plays a key role in the feedback regulation of cAMP signaling by limiting CRTC3 protein levels.Kim, Y.-H., Yoo, H., Hong, A.-R., Kwon, M., Kang, S.-W., Kim, K., Song, Y. NEDD4L limits cAMP signaling through ubiquitination of CREB-regulated transcription coactivator 3.</P>

A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype

Kim, Hyun Jin,Li, Qin,Tjon-Kon-Sang, Sandra,So, Insuk,Kiselyov, Kirill,Soyombo, Abigail A,Muallem, Shmuel Wiley (John WileySons) 2008 The EMBO journal Vol.27 No.8

<P>TRPML3 belongs to the TRPML subfamily of the transient receptor potential (TRP) channels. The A419P mutation in TRPML3 causes the varitint-waddler phenotype as a result of gain-of-function mutation (GOF). Regulation of the channels and the mechanism by which the A419P mutation leads to GOF are not known. We report here that TRPML3 is a Ca(2+)-permeable channel with a unique form of regulation by extracytosolic (luminal) H(+) (H(+)(e-cyto)). Regulation by H(+)(e-cyto) is mediated by a string of three histidines (H252, H273, H283) in the large extracytosolic loop between transmembrane domains (TMD) 1 and 2. Each of the histidines has a unique role, whereby H252 and H273 retard access of H(+)(e-cyto) to the inhibitory H283. Notably, the H283A mutation has the same phenotype as A419P and locks the channel in an open state, whereas the H283R mutation inactivates the channel. Accordingly, A419P eliminates regulation of TRPML3 by H(+)(e-cyto), and confers full activation to TRPML3(H283R). Activation of TRPML3 and regulation by H(+)(e-cyto) are altered by both the alpha-helix-destabilizing A419G and the alpha-helix-favouring A419M and A419K. These findings suggest that regulation of TRPML3 by H(+)(e-cyto) is due to an effect of the large extracytosolic loop on the orientation of fifth TMD and thus pore opening and show that the GOF of TRPML3(A419P) is due to disruption of this communication.</P>

Identification of Albula sp. (Albulidae: Albuliformes) Leptocephalus Collected from the Southern Coastal Waters of Korea using Cytochrome b DNA Sequences

Kim, Byung-Jik,Kim, Sung,Seo, Hyun-Seok,Oh, Jin-A The Korean Society of Oceanography 2008 Ocean science journal Vol.43 No.2

A single specimen of Albula leptocephalus (55.7 mm SL) was collected from the southern coastal waters of Korea using an aquatic lamp. It is characterized by having a ribbon-like body with a small head and a well-forked caudal fin. Although the general appearance was similar to the leptocephalus of A. vulpes including myomere counts and fin ray counts, the melanophore deposition was different from that of A. vulpes. This leptocephalus specimen was confirmed with A. forsteri using the cytochrome b mtDNA (Cytb) analysis. The genetic distance of Cytb between the present leptocephalus and A. forsteri is 0.006-0.038, which falls into the cutoff point separating Albula species into eight deep lineages including the four valid species. Its genetic characteristic have more similarities to those of Fiji than those of Hawaii and the Northern territory of Australia.

<i>SlPMEI</i>, a pollen-specific gene in tomato

Kim, Woong Bom,Lim, Chan Ju,Jang, Hyun A.,Yi, So Young,Oh, Sang-Keun,Lee, Ha Yeon,Kim, Hyun A.,Park, Youn-Il,Kwon, Suk-Yoon Canadian Science Publishing 2014 Canadian journal of plant science. Revue canadienn Vol.94 No.1

<P> Kim, W. B., Lim, C. J., Jang, H. A., Yi, S. Y., Oh, S.-K., Lee, H. Y., Kim, H. A., Park, Y.-I. and Kwon, S.-Y. 2014. SlPMEI, a pollen-specific gene in tomato. Can. J. Plant Sci. 94: 73-83. Pectin is one of the main components of plant cell walls, and its biosynthesis is controlled by pectin methylesterase (PME). Pectin methylesterase inhibitors (PMEIs) are key regulators of PME. We report here the cloning and characterization of a novel Solanum lycopersicum L. PMEI gene, SlPMEI. RT-PCR studies of leaf, seed, fruit, flower, and flower organs confirmed that SlPMEI is expressed specifically in pollen. Promoter analysis of SlPMEI revealed pollen-specific cis-acting elements (pollen lat52 and g10). In addition, SlPMEI is expressed independently of abiotic stress, pathogen exposure, and growth stage in tomato, and a histochemical analysis of promoter activity revealed pollen-specific expression in both Arabidopsis and tomato. Under the microscope, we observed pollen-specific GUS expression in the stamen of transgenic tomato plant. These results indicate that the promoter of SlPMEI has strong pollen-specific activity, and could therefore be useful for development of industrially and agronomically important transgenic plants. </P>

Suppression of Lipopolysaccharide-Induced Microglial Activation by a Benzothiazole Derivative

Kim, Eun-A,Kim, Han-Wook,Ahn, Jee-Yin,Hahn, Hoh-Gyu,Kim, Key-Sun,Kim, Tae-Ue,Cho, Sung-Woo Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.1

We previously reported that KHG21834, a benzothiazole derivative, attenuates the beta-amyloid (A${\beta}$)-induced degeneration of both cortical and mesencephalic neurons in vitro. Central nervous system inflammation mediated by activated microglia is a key event in the development of neurodegenerative disease. In this study, we show that KHG21834 suppresses inflammation-mediated cytokine upregulation. Specifically, KHG21834 induces significant reductions in the lipopolysaccharide-induced activation of microglia and production of proinflammatory mediators such as tumor necrosis factor-${\alpha}$, interlukin-1${\beta}$, nitric oxide, and inducible nitric oxide synthase. In addition, KHG21834 blocks the expression of mitogen-activated protein kinases, including ERK, p38 MAPK, JNK, and Akt. In vivo intracerebroventricular infusion of KHG21834 also leads to decreases the level of interleukin-1${\beta}$ and tumor necrosis factor-${\alpha}$ in brain. These results, in combination with our previous findings on A${\beta}$-induced degeneration, support the potential therapeutic efficacy of KHG21834 for the treatment of neurodegenerative disorders via the targeting of key glial activation pathways.

A multi-functional polyhydroxybutyrate nanoparticle for theranostic applications

Kwon, Hee-Su,Jung, Sung-Geun,Kim, Hae-Yeong,Parker, Stephanie A.,Batt, Carl A.,Kim, Young-Rok The Royal Society of Chemistry 2014 Journal of Materials Chemistry B Vol.2 No.25

<P>Biopolymer-based multi-functional nanoparticles have been developed through a one-step enzymatic polymerization reaction using engineered polyhydroxyalkanoate (PHA) synthase fused with green fluorescent protein (GFP) and a single chain variable fragment antibody (A33scFv) specific to colon cancer. PHA synthase possesses unique catalytic characteristics, namely covalent catalysis, by which the synthesized polyhydroxybutyrate chain remains covalently attached to the enzyme. The amphiphilic nature of the resulting protein-polymer hybrid gives rise to spontaneous self-assembly into a micellar structure with GFP and A33scFv displayed on the surface (AGPHB nanoparticle). A model compound, Nile red, was loaded into the hydrophobic core of the AGPHB nanoparticle during the polymerization and self-assembly process. The specificity of the fluorescent multi-functional AGPHB nanoparticle towards the colon cancer cell lines SW1222 (A33+) and HT29 (A33−) was confirmed and analysed quantitatively <I>in vitro</I>. This new biological approach provides a simple means of producing nanocarriers with a range of surface functionality and the sizes desired for imaging and targeted drug delivery.</P>

영화 <웰컴 투 동막골>에서 나타난 공동체의 특징 -장 뤽 낭시의 “무위의 공동체” 개념을 중심으로-

김상철 ( Sang Cheol Kim ),김진아 ( Jin A Kim ) 한양대학교 현대영화연구소 2015 현대영화연구 Vol.11 No.1

인류가 만들어온 대부분의 공동체들은 구성원 간의 연합이나 이익을 위해 동질성을 강조하며 강한 결집력을 보여 온 한편, 폐쇄성과 배타성이라는 한계를 드러내 왔다. 프랑스 철학자인 장 뤽 낭시는 이러한 전통적 개념의 공동체를 비판하며 새로운 대안적 원리로 동일성을 전제하지 않는 ‘무위의 공동체’개념을 제안하였다. ‘무위의 공동체’는 어떠한 목적을 위해 관계를 지향하는 것이 아니라, ‘함께 있음’ 그 자체가 가치가 되며, 공동체의 생산, 유지, 완성을 목표로 하지 않고, 존재 그 자체로 긍정의 관계를 만들어내며, 이를 통해 다른 존재의 변화를 일으키는 공동체이다. 본고는 영화 <웰컴 투 동막골>에서 나타난 공동체의 특징을 ‘무위의 공동체’ 개념을 중심으로 분석, 고찰한다. 이를 위해 먼저 전체주의적인 공동체의 특징을 살펴보며, 이를 해체하는 낭시의 ‘무위의 공동체’개념에 대해 논한다. 그리고 영화의 등장인물과 사건을 통해 동막골 공동체가 갖고 있는‘무위의 공동체’의 특성을 도출해 낸다. 영화의 배경이 되는 동막골은 인종, 언어, 사상, 이념이 부딪히고 개인적 특성들이 충돌하는, 철저한 갈등의 상황이 연출될 수밖에 없는 자리였다. 그러나 여기서 펼쳐진 공동체는 특정한 동질성을 강요하지 않고, 새로운 외부자가 들어오면 그들과 ‘함께 하며’ 자신들의 세계자체를 변화해간 공동체이다. 본고는 특히 외부인들의 견고한 내재성에 균열을 내어간 소수자들의 역할과 ‘죽음’을 통해 만들어간 동막골 공동체의 변화과정에 주목한다. 무위의 공동체 또는 동막골 공동체는 비록 현실에서는 실현이 어렵다 하더라도, 우리가 지향해야 할, 외부와 내부의 가름 없이 소통을 실천하는 공동체를 제시했다는 면에서 시사하는 바가 크다고 할 수 있다. Many human communities throughout history have emphasized social and cultural homogeneity to achieve common goals and preserve solidarity. However, this approach has also revealed limits, such as exclusivity and obstructiveness to outsiders. Rethinking the notion of community, Jean-Luc Nancy formulated the concept of “the inoperative community” to overcome these limits and present a new principle that does not assume homogeneity or unity. The inoperative community is the community that regards just “being together” itself as the primary value, so that relationships can exist even by virtue of doing nothing; these new or newly recognized relationships can then create changes in human existence. This paper examines characteristics of the community depicted in the South Korean film Welcome to DongMakGol(Directed by Park Kwang-hyun and produced by Jang Jin·Lee Eun-ha·Ji Sang-yong, 2005) from the perspective of Nancy`s inoperative community. First, it discusses the nature of totalitarian communities and the way the inoperative community deconstructs such traditional notions of communities. Then, it analyzes the community presented in DongMakGol as an inoperative community by analyzing characters and events in the movie. DongMakGol is a place in which a variety of racial, linguistic, ideological, and national identities collide, intersect, and conflict with one another. Since the DongMakGol community does not assume the possibility of a “pure” identity, it doesn`t require people to assimilate into any homogeneous social body and instead transforms itself when newcomers arrive, fostering a “being-together” with them. In particular, the treatment of minorities and “death” in this movie makes cracks in the solidity of immanence, so that these tropes perform a huge role in formulating a “being-together” community. Even though it is unrealistic to build an inoperative community like DongMakGol in real life, it is still meaningful to consider the model of the community we should pursue that it represents.

Oxidative lipid modification of nicastrin enhances amyloidogenic γ‐secretase activity in Alzheimer’s disease

Gwon, A‐,Ryeong,Park, Jong‐,Sung,Arumugam, Thiruma V.,Kwon, Yong‐,Kook,Chan, Sic L.,Kim, Seol‐,Hee,Baik, Sang‐,Ha,Yang, Sunghee,Yun, Young‐,Kwang,Choi, Yuri,Kim, Sa Blackwell Publishing Ltd 2012 AGING CELL Vol.11 No.4

<P><B>Summary</B></P><P>The cause of elevated level of amyloid β‐peptide (Aβ42) in common late‐onset sporadic [Alzheimer’s disease (AD)] has not been established. Here, we show that the membrane lipid peroxidation product 4‐hydroxynonenal (HNE) is associated with amyloid and neurodegenerative pathologies in AD and that it enhances γ‐secretase activity and Aβ42 production in neurons. The γ‐secretase substrate receptor, nicastrin, was found to be modified by HNE in cultured neurons and in brain specimens from patients with AD, in which HNE–nicastrin levels were found to be correlated with increased γ‐secretase activity and Aβ plaque burden. Furthermore, HNE modification of nicastrin enhanced its binding to the γ‐secretase substrate, amyloid precursor protein (APP) C99. In addition, the stimulation of γ‐secretase activity and Aβ42 production by HNE were blocked by an HNE‐scavenging histidine analog in a 3xTgAD mouse model of AD. These findings suggest a specific molecular mechanism by which oxidative stress increases Aβ42 production in AD and identify HNE as a novel therapeutic target upstream of the γ‐secretase cleavage of APP.</P>

부산지역 유흥업소 종사여성으로부터 분리된 HPV16형의 발암유전자(E6/E7) 돌연변이 유형 분석

민상기(Sang-Kee Min),김성순(Sung Soon Kim),최병선(Byeong-Sun Choi),장대호(Dai-Ho Jang),이미옥(Mee-Ok Lee),최성화(Seung-Hwa Choi),김남호(Nam-Ho Kim),박연경(Yon-Koung Park),정영아(Yeong-A Jeong),김성준(Seong-Joon Kim),빈재훈(Jae-Hun Bi 한국생명과학회 2009 생명과학회지 Vol.19 No.6

HPV-16형의 염기배열 변이는 지역적, 인종적으로 특징적인 차이가 있으며 특히 HPV-16형 E6/E7 유전자의 특정 염기서열변이는 자궁경부암 및 자궁상피내 신생종양물의 발생을 일으키는 고위험 요인으로 알려져 있다. 본 연구는 2007년 부산지역 유흥업소 종사여성으로 분리된 HPV-16형 19건을 대상으로 E6/E7 유전자 영역(nt 34-880)을 표적으로 지역적 염기서열 변이를 조사하였다. nucleotide 수준에서 HPV16형 E6 유전자는 T178G (n=11), T178A (n=1), T350G (n=4), A442C (n=2), A104T, A111G, C116T, G145T, T183G, C335T, G522C 등 11종의 변이주가 발견되었고, E7 유전자는 A647G (n=12), A645C, A777C, G663A, T732C, T760C, A775T, T789C, T795G 등 9종의 변이주가 발견되었다. 아미노산 수준에서는 HPV-16형 E6 단백질의 경우 D25E (n=12), L83V (n=4), E113D (n=2), M1L, Q3R, P5S, Q14H, D25N, I27R, H78Y, C140S 등 11종의 변이주를, HPV16형 E7 단백질의 경우 N29S (n=12), L28F, T72S 등 3종의 변이주를 관찰할 수 있었다. 본 연구 결과, 부산지역의 HPV-16형 E6/E7 우점 돌연변이주는 E6 D25E (75%), E7 N29S (78%)로 각각 나타났다. 앞으로 자궁경부암 환자 및 일반여성을 포함한 더 많은 모집단을 대상으로 HPV-16형 E6/E7의 intratypic variants를 비교 조사하여 실제 HPV-16형 E6/E7 어떤 변이주가 자궁경부암 유발 위험성과의 관련성은 더 많이 연구되어져야 할 것으로 사료된다. Recent studies have reported that the distribution of HPV-16 sequence variation differs geographically, and more specifically that HPV-16 E6/E7 intratypic variants might carry a high risk for development of ICC (invasive cervical cancer) and CIN (cervical intraepithelial neoplasia) in a given population. To investigate the genetic diversities of HPV-16 E6/E7 oncogene by region, we collected nineteen HPV-16 isolates from sexually high-risk women in Busan, and analyzed the HPV-16 E6/E7 coding regions (nt 34 to 880) with HPV-16 E6/E7 specific PCR amplification. At the nucleotide level, eleven variants of the E6 genes and nine variants of the E7 genes were identified as follows: E6 T178G (n=11), E6 T178A (n=1), E6 T350G (n=3), E6 A442C (n=2), E6 A104T, E6 A111G, E6 C116T, E6 G145T, E6 T183G, E6 C335T, E6 G522C and E7 A647G (n=12), E7 A645C, E7 A777C, E7 G663A, E7 T732C, E7 T760C, E7 A775T, E7 T789C and E7 T795G, respectively. At the amino acid level, the isolated HPV-16 E6 and E7 genes showed eleven E6 variants: E6 D25E (n=12), E6 L83V (n=4), E6 E113D (n=2), E6 M1L, E6 Q3R, E6 P5S, E6 Q14H, E6 D25N, E6 I27R, E6 H78Y, E6 C140S and three E7 variants: N29S (n=12), L28F, T72S. HPV16 E6 L83V, the dominant variant in the Caucasian population, showed relatively low frequencies in our study population. We elucidated that the dominant HPV-16 E6/E7 variants were HPV-16 E6 D25E (63.2%) and HPV-16 E7 N29S (63.2%), which were phylogenetically included in Asian lineage. Further study is needed to evaluate the risk of cervical cancer related HPV-16 E6/E7 intratypic variants in the Korean population.

Biochanin A의 미백 효과에 관한 연구

박성하 ( Sung Ha Park ),김아현 ( A Hyun Kim ),박병준 ( Byoung Jun Park ),김진준 ( Jin Jun Kim ) 대한화장품학회 2013 대한화장품학회지 Vol.39 No.4

본 연구는 미백 소재 개발을 위하여 강진향(Dalbergia odorifera T. Chen) 추출물에서 분리한 활성물질인 biochanin A의 멜라닌 생성에 연관된 효과를 알아보았다. Biochanin A는 B16F1 melanoma 세포에서 농도의존적으로 멜라닌 양을 억제하였으며, 멜라닌 생합성 저해 효과는 10 μg/mL 농도에서 멜라닌 생성 억제율이 48%로 나타났다. Western blot을 이용하여 microphthalmia associated transcription factor (MITF), Tyrosinase, Trp-1와 Trp-2의 발현을 억제함을 확인하였다. 따라서 biochanin A는 미백 효능을 갖는 화장품 소재로서의 개발 가능성이 클 것으로 기대된다. To develop a new whitening agent for cosmetics, we investigated the inhibitory effects of biochanin A on melanogenesis. The biochanoin A is an active component in the extracts of Dalbergia odorifera T. Chen. It reduced melanin contents of B16F1 melanoma cells in a dose-dependent manner and decreased to about 48% at a concentration 10 μg/mL. It also inhibited the expression in microphthalmia associated transcription factor (MITF), Tyrosinase, Tyrosinase related protein 1 (Trp-1), and Tyrosinase related protein 2 (Trp-2) in melanocytes. The results suggested that biochanin A has considerable potential as a cosmetics ingredient with a whitening effect.