@article{92ab09dee9964204bcbc8461004e4637,
title = "DIRAS3 (ARHI) Blocks RAS/MAPK Signaling by Binding Directly to RAS and Disrupting RAS Clusters",
abstract = "Sutton et. al. show that re-expression of DIRAS3 can inhibit the growth of multiple cancer types driven by K-RAS mutations by a direct interaction and disruption of K-RAS higher ordered clusters. This phenotype is driven by an N-terminal extension, which distinguishes DIRAS3 from other RAS-related small GTPases.",
keywords = "ARHI, DIRAS3, RAS inhibitor, cluster, dimer, heteromer, ovarian cancer, pancreatic cancer, transformation",
author = "Sutton, {Margie N.} and Zhen Lu and Li, {Yao Cheng} and Yong Zhou and Tao Huang and Reger, {Albert S.} and Hurwitz, {Amy M.} and Timothy Palzkill and Craig Logsdon and Xiaowen Liang and Gray, {Joe W.} and Xiaolin Nan and John Hancock and Wahl, {Geoffrey M.} and Bast, {Robert C.}",
note = "Funding Information: The authors would like to thank members of the Bast laboratory for their discussion and suggestions and Dr. Robert Langley for careful review of the manuscript. The Protein Production and Analysis Core at IBT of Texas A&M University provided services for molecular cloning and partial purification of the KRAS and DIRAS3 recombinant proteins, and Dr. Chun Li in the Department of Cancer Systems Imaging provided access to the Biacore 3000 instrument. This work was supported by the MD Anderson SPOREs in Ovarian Cancer grants NCI P50 CA 83639 and CA 217685 ; the National Cancer Institute grant R01 CA135354 ; a grant from the Cancer Prevention and Research Institute of Texas ( RP140429 ); the Shared Resources of the MD Anderson CCSG grant NCI P30 CA16672 ; The National Foundation for Cancer Research ; philanthropic support from the Anne and Henry Zarrow Foundation ; and generous donations from Stuart and Gaye-Lynn Zarrow , the Mossy Foundation , and the Roberson endowment . M.N.S. was supported by a pre-doctoral fellowship from NIH TL1TR000369 and UL1TF000371 and a fellowship in cancer research from the American Legion Auxiliary as well as the Ann and Sol Schreiber Mentored Investigator Award from the Ovarian Cancer Research Fund Alliance . SPR studies were conducted in the Protein Production and Analysis Core at Texas A&M IBT. This work was performed in partial fulfillment of the requirements for a PhD degree from The University of Texas MD Anderson UTHeath GSBS, Houston, TX 77030, USA. Funding Information: The authors would like to thank members of the Bast laboratory for their discussion and suggestions and Dr. Robert Langley for careful review of the manuscript. The Protein Production and Analysis Core at IBT of Texas A&M University provided services for molecular cloning and partial purification of the KRAS and DIRAS3 recombinant proteins, and Dr. Chun Li in the Department of Cancer Systems Imaging provided access to the Biacore 3000 instrument. This work was supported by the MD Anderson SPOREs in Ovarian Cancer grants NCI P50 CA 83639 and CA 217685; the National Cancer Institute grant R01 CA135354; a grant from the Cancer Prevention and Research Institute of Texas (RP140429); the Shared Resources of the MD Anderson CCSG grant NCI P30 CA16672; The National Foundation for Cancer Research; philanthropic support from the Anne and Henry Zarrow Foundation; and generous donations from Stuart and Gaye-Lynn Zarrow, the Mossy Foundation, and the Roberson endowment. M.N.S. was supported by a pre-doctoral fellowship from NIH TL1TR000369 and UL1TF000371 and a fellowship in cancer research from the American Legion Auxiliary as well as the Ann and Sol Schreiber Mentored Investigator Award from the Ovarian Cancer Research Fund Alliance. SPR studies were conducted in the Protein Production and Analysis Core at Texas A&M IBT. This work was performed in partial fulfillment of the requirements for a PhD degree from The University of Texas MD Anderson UTHeath GSBS, Houston, TX 77030, USA. M.N.S. Z.L. and R.C.B. designed the study. M.N.S. Y.-C.L. Y.Z. and T.H. carried out experiments. X.L. performed SPR analysis. Y.-C.L. A.S.R. A.M.H. T.P. C.L. J.W.G. X.N. J.H. G.M.W. and R.C.B. provided resources and reagents. M.N.S. Z.L. Y.-C.L. G.M.W. and R.C.B. analyzed the data, and M.N.S. and R.C.B. wrote the manuscript. All authors edited and approved the manuscript. The authors declare no conflict of interest. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = dec,
day = "10",
doi = "10.1016/j.celrep.2019.11.045",
language = "English (US)",
volume = "29",
pages = "3448--3459.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}