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2. Structure–function analysis of the SHOC2–MRAS–PP1C holophosphatase complex

Author

Kwon, Jason J, Hajian, Behnoush, Bian, Yuemin, Young, Lucy C, Amor, Alvaro J, Fuller, James R, Fraley, Cara V, Sykes, Abbey M, So, Jonathan, Pan, Joshua, Baker, Laura, Lee, Sun Joo, Wheeler, Douglas B, Mayhew, David L, Persky, Nicole S, Yang, Xiaoping, Root, David E, Barsotti, Anthony M, Stamford, Andrew W, Perry, Charles K, Burgin, Alex, McCormick, Frank, Lemke, Christopher T, Hahn, William C, and Aguirre, Andrew J

Subjects
2.1 Biological and endogenous factors, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, Generic health relevance, Cancer, Amino Acid Motifs, Binding Sites, Cryoelectron Microscopy, Guanosine Triphosphate, Humans, Intracellular Signaling Peptides and Proteins, MAP Kinase Signaling System, Multiprotein Complexes, Mutation, Missense, Phosphorylation, Protein Binding, Protein Phosphatase 1, Protein Stability, raf Kinases, ras Proteins, General Science & Technology
Abstract

Receptor tyrosine kinase (RTK)-RAS signalling through the downstream mitogen-activated protein kinase (MAPK) cascade regulates cell proliferation and survival. The SHOC2-MRAS-PP1C holophosphatase complex functions as a key regulator of RTK-RAS signalling by removing an inhibitory phosphorylation event on the RAF family of proteins to potentiate MAPK signalling1. SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations in this complex result in congenital RASopathy syndromes2-5. However, the structure and assembly of this complex are poorly understood. Here we use cryo-electron microscopy to resolve the structure of the SHOC2-MRAS-PP1C complex. We define the biophysical principles of holoenzyme interactions, elucidate the assembly order of the complex, and systematically interrogate the functional consequence of nearly all of the possible missense variants of SHOC2 through deep mutational scanning. We show that SHOC2 binds PP1C and MRAS through the concave surface of the leucine-rich repeat region and further engages PP1C through the N-terminal disordered region that contains a cryptic RVXF motif. Complex formation is initially mediated by interactions between SHOC2 and PP1C and is stabilized by the binding of GTP-loaded MRAS. These observations explain how mutant versions of SHOC2 in RASopathies and cancer stabilize the interactions of complex members to enhance holophosphatase activity. Together, this integrative structure-function model comprehensively defines key binding interactions within the SHOC2-MRAS-PP1C holophosphatase complex and will inform therapeutic development .

Published
2022

5. From the Beginning of the Korean Gynecologic Oncology Group to the Present and Next Steps.

Author

Min, Kyung-Jin, Kim, Nam Kyeong, Song, Jae-Yun, Choi, Min Chul, Lee, Shin Wha, Lee, Keun Ho, Kim, Min Kyu, Kang, Sokbom, Choi, Chel Hun, Lee, Jeong-Won, Lee, Eun-Ju, Eom, Keun-Yong, Kim, Sang Wun, Cho, Hanbyoul, Lee, Sun Joo, Lim, Myong Cheol, Bae, Jaeman, Yoo, Chong Woo, Kim, Kidong, and Kim, Dae-Yeon

Subjects
MEDICAL protocols, INTERPROFESSIONAL relations, ONCOLOGY, INTERNATIONAL agencies, FEMALE reproductive organ tumors, GYNECOLOGY, INSTITUTIONAL cooperation, MEDICAL research, ORGANIZATIONAL goals
Abstract

Simple Summary: Established in 2002, the Korean Gynecologic Oncology Group (KGOG) has presented improved clinical outcomes based on multi-center clinical trials. To date, KGOG has approved 156 studies and published 68 KGOG-led studies. The organization aims to advance gynecologic cancer research through sustained efforts and international collaboration. The Korean Gynecologic Oncology Group (KGOG) was established in 2002 and is the only organization in Korea conducting multi-center clinical trials for gynecologic cancers. Since its re-establishment as a non-profit organization in 2021, KGOG has grown significantly, now including 207 gynecologic oncology specialists from 76 hospitals. This growth is a testament to the dedication and hard work of all those involved in the organization. KGOG is committed to maximizing the activation of multi-center clinical research through policies that support patients with rare diseases and gynecologic cancer research, focusing on strengthening institutional capacity, equalizing participation opportunities, and enhancing information sharing. A significant milestone for KGOG was becoming a member of the US Gynecologic Oncology Group (GOG) in 2005, allowing participation in GOG clinical trials. KGOG later joined the Gynecologic Cancer InterGroup (GCIG) and strengthened its capabilities by hosting the first Endometrial Cancer Consensus Conference—Clinical Research (ECCC-CR) in 2023. KGOG holds biannual meetings and symposia, as well as 224 operating committee meetings annually to review the discussions of the Tumor Site Committee. KGOG has conducted 156 investigator-initiated trial (IIT) or sponsor-initiated trial (SIT) studies as KGOG-led or participated in research. Currently, 18 studies are registered, and 10 are in preparation. To date, 68 papers have been published. KGOG conducts six national projects and collaborates with external organizations such as the NRG Oncology Foundation, Gynecologic Oncology Group Partners (GOG-P), GCIG, East Asian Gynecologic Oncology Trial group (EAGOT), and the Japanese Gynecologic Oncology Group (JGOG). Through collaboration with renowned international research institutions, KGOG has significantly expanded the scope of its research, achieving noteworthy clinical outcomes. This report not only introduces the history and recent status of KGOG but also presents the exciting future direction of the organization, filled with potential breakthroughs and advancements in gynecologic oncology research. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Figure S6 from Hypoxia Selectively Enhances Integrin α5β1 Receptor Expression in Breast Cancer to Promote Metastasis

Author

Ju, Julia A., primary, Godet, Inês, primary, Ye, I Chae, primary, Byun, Jungmin, primary, Jayatilaka, Hasini, primary, Lee, Sun Joo, primary, Xiang, Lisha, primary, Samanta, Debangshu, primary, Lee, Meng Horng, primary, Wu, Pei-Hsun, primary, Wirtz, Denis, primary, Semenza, Gregg L., primary, and Gilkes, Daniele M., primary

Published
2023
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36. Supplemental Table 1 from Hypoxia Selectively Enhances Integrin α5β1 Receptor Expression in Breast Cancer to Promote Metastasis

Author

Ju, Julia A., primary, Godet, Inês, primary, Ye, I Chae, primary, Byun, Jungmin, primary, Jayatilaka, Hasini, primary, Lee, Sun Joo, primary, Xiang, Lisha, primary, Samanta, Debangshu, primary, Lee, Meng Horng, primary, Wu, Pei-Hsun, primary, Wirtz, Denis, primary, Semenza, Gregg L., primary, and Gilkes, Daniele M., primary

Published
2023
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37. Supplemental Legends from Hypoxia Selectively Enhances Integrin α5β1 Receptor Expression in Breast Cancer to Promote Metastasis

Author

Ju, Julia A., primary, Godet, Inês, primary, Ye, I Chae, primary, Byun, Jungmin, primary, Jayatilaka, Hasini, primary, Lee, Sun Joo, primary, Xiang, Lisha, primary, Samanta, Debangshu, primary, Lee, Meng Horng, primary, Wu, Pei-Hsun, primary, Wirtz, Denis, primary, Semenza, Gregg L., primary, and Gilkes, Daniele M., primary

Published
2023
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38. Data from Targeted Gene Silencing Using RGD-Labeled Chitosan Nanoparticles

Author

Han, Hee Dong, primary, Mangala, Lingegowda S., primary, Lee, Jeong Won, primary, Shahzad, Mian M.K., primary, Kim, Hye Sun, primary, Shen, Deyu, primary, Nam, Eun Ji, primary, Mora, Edna M., primary, Stone, Rebecca L., primary, Lu, Chunhua, primary, Lee, Sun Joo, primary, Roh, Ju Won, primary, Nick, Alpa M., primary, Lopez-Berestein, Gabriel, primary, and Sood, Anil K., primary

Published
2023
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39. Supplementary Figures 1 - 3 from Biologic Effects of Platelet-Derived Growth Factor Receptor α Blockade in Uterine Cancer

Author

Roh, Ju-Won, primary, Huang, Jie, primary, Hu, Wei, primary, Yang, XiaoYun, primary, Jennings, Nicholas B., primary, Sehgal, Vasudha, primary, Sohn, Bo Hwa, primary, Han, Hee Dong, primary, Lee, Sun Joo, primary, Thanapprapasr, Duangmani, primary, Bottsford-Miller, Justin, primary, Zand, Behrouz, primary, Dalton, Heather J., primary, Previs, Rebecca A., primary, Davis, Ashley N., primary, Matsuo, Koji, primary, Lee, Ju-Seog, primary, Ram, Prahlad, primary, Coleman, Robert L., primary, and Sood, Anil K., primary

Published
2023
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40. Supplementary Data from EphA2 Targeted Chemotherapy Using an Antibody Drug Conjugate in Endometrial Carcinoma

Author

Lee, Jeong-Won, primary, Stone, Rebecca L., primary, Lee, Sun Joo, primary, Nam, Eun Ji, primary, Roh, Ju-Won, primary, Nick, Alpa M., primary, Han, Hee-Dong, primary, Shahzad, Mian M.K., primary, Kim, Hye-Sun, primary, Mangala, Lingegowda S., primary, Jennings, Nicholas B., primary, Mao, Shenlan, primary, Gooya, John, primary, Jackson, Dowdy, primary, Coleman, Robert L., primary, and Sood, Anil K., primary

Published
2023
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41. Data from Functional Roles of Src and Fgr in Ovarian Carcinoma

Author

Kim, Hye-Sun, primary, Han, Hee Dong, primary, Armaiz-Pena, Guillermo N., primary, Stone, Rebecca L., primary, Nam, Eun Ji, primary, Lee, Jeong-Won, primary, Shahzad, Mian M. K., primary, Nick, Alpa M., primary, Lee, Sun Joo, primary, Roh, Ju-Won, primary, Nishimura, Masato, primary, Mangala, Lingegowda S., primary, Bottsford-Miller, Justin, primary, Gallick, Gary E., primary, Lopez-Berestein, Gabriel, primary, and Sood, Anil K., primary

Published
2023
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42. Supplementary Data from Targeted Gene Silencing Using RGD-Labeled Chitosan Nanoparticles

Author

Han, Hee Dong, primary, Mangala, Lingegowda S., primary, Lee, Jeong Won, primary, Shahzad, Mian M.K., primary, Kim, Hye Sun, primary, Shen, Deyu, primary, Nam, Eun Ji, primary, Mora, Edna M., primary, Stone, Rebecca L., primary, Lu, Chunhua, primary, Lee, Sun Joo, primary, Roh, Ju Won, primary, Nick, Alpa M., primary, Lopez-Berestein, Gabriel, primary, and Sood, Anil K., primary

Published
2023
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43. Supplementary Figures S1-S5 from Functional Roles of Src and Fgr in Ovarian Carcinoma

Author

Kim, Hye-Sun, primary, Han, Hee Dong, primary, Armaiz-Pena, Guillermo N., primary, Stone, Rebecca L., primary, Nam, Eun Ji, primary, Lee, Jeong-Won, primary, Shahzad, Mian M. K., primary, Nick, Alpa M., primary, Lee, Sun Joo, primary, Roh, Ju-Won, primary, Nishimura, Masato, primary, Mangala, Lingegowda S., primary, Bottsford-Miller, Justin, primary, Gallick, Gary E., primary, Lopez-Berestein, Gabriel, primary, and Sood, Anil K., primary

Published
2023
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44. Supplementary Figure 1 from Converging Evidence for Efficacy from Parallel EphB4-Targeted Approaches in Ovarian Carcinoma

Author

Spannuth, Whitney A., primary, Mangala, Lingegowda S., primary, Stone, Rebecca L., primary, Carroll, Amy R., primary, Nishimura, Masato, primary, Shahzad, Mian M.K., primary, Lee, Sun-Joo, primary, Moreno-Smith, Myrthala, primary, Nick, Alpa M., primary, Liu, Ren, primary, Jennings, Nicholas B., primary, Lin, Yvonne G., primary, Merritt, William M., primary, Coleman, Robert L., primary, Vivas-Mejia, Pablo E., primary, Zhou, Yue, primary, Krasnoperov, Valery, primary, Lopez-Berestein, Gabriel, primary, Gill, Parkash S., primary, and Sood, Anil K., primary

Published
2023
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45. Data from Biologic Effects of Platelet-Derived Growth Factor Receptor α Blockade in Uterine Cancer

Author

Roh, Ju-Won, primary, Huang, Jie, primary, Hu, Wei, primary, Yang, XiaoYun, primary, Jennings, Nicholas B., primary, Sehgal, Vasudha, primary, Sohn, Bo Hwa, primary, Han, Hee Dong, primary, Lee, Sun Joo, primary, Thanapprapasr, Duangmani, primary, Bottsford-Miller, Justin, primary, Zand, Behrouz, primary, Dalton, Heather J., primary, Previs, Rebecca A., primary, Davis, Ashley N., primary, Matsuo, Koji, primary, Lee, Ju-Seog, primary, Ram, Prahlad, primary, Coleman, Robert L., primary, and Sood, Anil K., primary

Published
2023
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46. Supplementary Figure 2 from Metronomic Activity of CD44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma

Author

Lee, Sun Joo, primary, Ghosh, Sukhen C., primary, Han, Hee Dong, primary, Stone, Rebecca L., primary, Bottsford-Miller, Justin, primary, Shen, De Yue, primary, Auzenne, Edmond J., primary, Lopez-Araujo, Alejandro, primary, Lu, Chunhua, primary, Nishimura, Masato, primary, Pecot, Chad V., primary, Zand, Behrouz, primary, Thanapprapasr, Duangmani, primary, Jennings, Nicholas B, primary, Kang, Yu, primary, Huang, Jie, primary, Hu, Wei, primary, Klostergaard, Jim, primary, and Sood, Anil K., primary

Published
2023
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47. Supplementary Figure 1 from Metronomic Activity of CD44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma

Author

Lee, Sun Joo, primary, Ghosh, Sukhen C., primary, Han, Hee Dong, primary, Stone, Rebecca L., primary, Bottsford-Miller, Justin, primary, Shen, De Yue, primary, Auzenne, Edmond J., primary, Lopez-Araujo, Alejandro, primary, Lu, Chunhua, primary, Nishimura, Masato, primary, Pecot, Chad V., primary, Zand, Behrouz, primary, Thanapprapasr, Duangmani, primary, Jennings, Nicholas B, primary, Kang, Yu, primary, Huang, Jie, primary, Hu, Wei, primary, Klostergaard, Jim, primary, and Sood, Anil K., primary

Published
2023
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48. Supplementary Methods from Metronomic Activity of CD44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma

Author

Lee, Sun Joo, primary, Ghosh, Sukhen C., primary, Han, Hee Dong, primary, Stone, Rebecca L., primary, Bottsford-Miller, Justin, primary, Shen, De Yue, primary, Auzenne, Edmond J., primary, Lopez-Araujo, Alejandro, primary, Lu, Chunhua, primary, Nishimura, Masato, primary, Pecot, Chad V., primary, Zand, Behrouz, primary, Thanapprapasr, Duangmani, primary, Jennings, Nicholas B, primary, Kang, Yu, primary, Huang, Jie, primary, Hu, Wei, primary, Klostergaard, Jim, primary, and Sood, Anil K., primary

Published
2023
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49. Supplementary Figure 3 from Metronomic Activity of CD44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma

Author

Lee, Sun Joo, primary, Ghosh, Sukhen C., primary, Han, Hee Dong, primary, Stone, Rebecca L., primary, Bottsford-Miller, Justin, primary, Shen, De Yue, primary, Auzenne, Edmond J., primary, Lopez-Araujo, Alejandro, primary, Lu, Chunhua, primary, Nishimura, Masato, primary, Pecot, Chad V., primary, Zand, Behrouz, primary, Thanapprapasr, Duangmani, primary, Jennings, Nicholas B, primary, Kang, Yu, primary, Huang, Jie, primary, Hu, Wei, primary, Klostergaard, Jim, primary, and Sood, Anil K., primary

Published
2023
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50. Supplementary Figure 2 from Biological Roles of the Delta Family Notch Ligand Dll4 in Tumor and Endothelial Cells in Ovarian Cancer

Author

Hu, Wei, primary, Lu, Chunhua, primary, Dong, Han Hee, primary, Huang, Jie, primary, Shen, De-yu, primary, Stone, Rebecca L., primary, Nick, Alpa M., primary, Shahzad, Mian M.K., primary, Mora, Edna, primary, Jennings, Nicholas B., primary, Lee, Sun Joo, primary, Roh, Ju-Won, primary, Matsuo, Koji, primary, Nishimura, Masato, primary, Goodman, Blake W., primary, Jaffe, Robert B., primary, Langley, Robert R., primary, Deavers, Michael T., primary, Lopez-Berestein, Gabriel, primary, Coleman, Robert L., primary, and Sood, Anil K., primary

Published
2023
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