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The N-Degron Pathway Mediates ER-phagy
Ji, Chang Hoon,Kim, Hee Yeon,Heo, Ah Jung,Lee, Su Hyun,Lee, Min Ju,Kim, Su Bin,Srinivasrao, Ganipisetti,Mun, Su Ran,Cha-Molstad, Hyunjoo,Ciechanover, Aaron,Choi, Cheol Yong,Lee, Hee Gu,Kim, Bo Yeon,Kw Elsevier 2019 Molecular Cell Vol.75 No.5
<P><B>Summary</B></P> <P>The endoplasmic reticulum (ER) is susceptible to wear-and-tear and proteotoxic stress, necessitating its turnover. Here, we show that the N-degron pathway mediates ER-phagy. This autophagic degradation initiates when the transmembrane E3 ligase TRIM13 (also known as RFP2) is ubiquitinated via the lysine 63 (K63) linkage. K63-ubiquitinated TRIM13 recruits p62 (also known as sequestosome-1), whose complex undergoes oligomerization. The oligomerization is induced when the ZZ domain of p62 is bound by the N-terminal arginine (Nt-Arg) of arginylated substrates. Upon activation by the Nt-Arg, oligomerized TRIM13-p62 complexes are separated along with the ER compartments and targeted to autophagosomes, leading to lysosomal degradation. When protein aggregates accumulate within the ER lumen, degradation-resistant autophagic cargoes are co-segregated by ER membranes for lysosomal degradation. We developed synthetic ligands to the p62 ZZ domain that enhance ER-phagy for ER protein quality control and alleviate ER stresses. Our results elucidate the biochemical mechanisms and pharmaceutical means that regulate ER homeostasis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The autophagic adaptor p62 mediates autophagic degradation of the ER (ER-phagy) </LI> <LI> The ER membrane E3 ligase TRIM13 is a ubiquitin-dependent ER-phagy receptor to p62 </LI> <LI> N-terminal arginylation is an ER-phagy degron via binding to the ZZ domain of p62 </LI> <LI> p62-TRIM13-Nt-Arg circuit mediates ER protein quality control and homeostasis </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
특발성 혈소판 감소성 자반증이 있는 초산모에서 전자간증 합병후 발생한 분만기주위 심근증
손창업 ( Chang Up Son ),강경화 ( Kyoung Hwa Kang ),나우석 ( Woo Suk Na ),정민 ( Min Choung ),류지훈 ( Ji Hoon Ryu ),민병강 ( Byoung Kang Min ),김기환 ( Ki Hwan Kim ),이병관 ( Byung Kwan Lee ),노정훈 ( Jeong Hoon Rho ),오관영 ( Kw 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.7
Peripartum cardiomyopathy is a dilated cardiomyopathy of unexplained cause that occurs during the last trimester of pregnancy or within 5 months after delivery. And, It is a rare disease that has a frequency of 1 in 1,300-15,000 deliveries. It has not yet been reported that peripartum cardiomyopathy has occurred in an preeclampsia woman superimposed on idiopathic thrombocytopenic purpura. Moreover, the association between idiopathic thrombocytopenic purpura and peripartum cardiomyopathy has not been studied. Recently, we experienced a case of a woman who has undergone emergency Cesarean section due to complicated severe preeclampsia superimposed on idiopathic thrombocytopenic purpura. On the postoperative day, this patient developed respiratory distress and pulmonary edema. Peripartum cardiomyopathy was diagnosed by echocardiography and we present with a brief review of literatures.
장기훈(KH Chang),임옥룡(OR Lim),오민정(MJ Oh),이은의(EY Lee),이희경(HK Lee),이규완(KW Lee) 대한산부인과학회 1994 Obstetrics & Gynecology Science Vol.37 No.12
The endoermal sinus tumor of ovary is originated from the undifferentiated primitive germ cell of the embryonal stage . This tumor developed in next to the dysgerminoma of the ovarian malignant germ cell tumors and is highly malignant and fatal and very rare. We experinced one case of the endodermal sinus tumor of ovary in 20 year old woman, who had complaint with abdominal distension and low abdominal pain. So we report the case of brief review of literatures.
장기훈(KH Chang),임옥룡(OR Lim),정경효(KH Chung),이찬(C Lee),김영태(YT Kim),이규완(KW Lee) 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.6
Gastroschisis is intestinal herniation through a defect in the anterior abdominal wall, usually to the right of the umbilicus. There is no sac and the intestines are covered with a thickened inflammatory exudate. This anomaly is identified in prehaps 1 in 10000 births. Most cases of gastroschisis occur sporadically and chromosomal anomalies are less common. However, about one forth of musculoskeletal and gastrointestinal abnormalties. The prognosis is good for the fetus who wheighs more than 1500 gm and has no associated anomalies, provided surgical correction is achieved rapidly. A case of gastroschisis diagnosed by ultrasonography is reported with a biref review of the literatures.
자궁육종에 있어서 DNA Flow Cytometry의 의의
장기훈(KH Chang),이용호(YH Lee),김종오(JO Kim),신재철(JC Shin),이규완(KW Lee) 대한산부인과학회 1996 Obstetrics & Gynecology Science Vol.39 No.9
The most important predictor of survival in uterine sarcoma is considered to be surgical stage followed by grade of differentiation and frequency of mitotic counts. During the past decade DNA analysis has proven to be powerful prognostic tool for a variety of human malignancies. Flow cytometry of various gynecological tumors such as ovary, uterine corpus, and uterine cervix has shown that aneuploid tumors and those with high S-phase rate carry a worse prognosis than diploid tumors or those with a low S-phase. The aim of this study is to investigate the prognostic importance of DNA ploidy adn S-phase rate relation to previously-known prognostic factors in 9 patients with uterine sarcoma.
이낙우(NW Lee),장기훈(KH Chang),김용민(YM Kim),김해중(HJ Kim),이규완(KW Lee) 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.7
The thirty three cases of ovarian tumors in pregnancy among 9537 women were reviewd clinically at the Department of Obstetrics and Gynecology, College of Medicine, Korea University The result obtained were as follows; 1. The incidence of ovarian tumors in pregnancy was 1 in 289 deliveries. 2. Mean age was 27.9 years old and the range was 20-35 years old. 3. Mean parity was 0.4 4. According to clinical manifestation, a free of symptoms and sings in 20 cases (60.6%), low abdominal pain in 9 cases(27.3%) vaginal bleeding in 3 cases (9.1%) and palpable mass in 1 case(3.0%) were formed. 5. As to the size of tumor 15 cases(45.5%), were 5-6cm in diameter, 13 cases(39.4%) were 7-10cm , 2 cases (6.0%) were 11-15cm and 3 cases(9.1%) were over 16cm 6. Among the reviewed cases 32 cases(97.0%) were unilateral and 1 case(3.0%) was bilateral. 7. As the timing of diagnosis, 48.5% was diagnosed in the 1st trimester, 9.1% in the 2nd trimester, 42.4% in the 3rd trimester. 8. According to the method of diagonsis, known ovarian tumors were 4 cases(12.1%) 16 cases(48.5%), were found by physical examination and ultrasonography and 13 cases(39.4%) were incidental finding during cesarean section. 9. According to histopathologic type, benign cystic teratoma was 7 cases (23.3%) simple cyst was 5 cases (16.7%) mucinous cystandenoma was 4 cases (13.4%) corpus leteum cyst was 4 cases (13.4%) endometrial cyst was 3 cases(10.0%) seruous cystadenoma was 2 cases(6.7%) parovarian cyst, serousmucinous cystadenoma, theca lutein cyst, Blood filled undetermined cyst was 1 case (3.3%) repectively. One case of malignant ovarian tumor was dysgerminoma. 10. As a complicated cases, the torsion of tumor was formed in 2 cases (6.0%) and the rupture of tumor was formed 1 case(3.0%). 11. Conservative ovarian cystectomy was performed in 13 cases(44.8%) unilateral salpingoophrectory in 13 cases (44.8%) , unilateral oophrectomy in 3 cases(6.9%) and ovarian wedge resection in 1 case(3.5%). 12. Outcome of pregnancy and mode of delivery : Fourteen cases(70%) were followed up. Among them, term delivry in 8 cases (40.0%) among them vaginal delivery in 2 case(25.0%) cesarean section in 6 cases(75%) and artificial abortin in 6 cases(30.0%) were occured. Lost follow up cases were 6 cases(30.0%).