@article{4520b511ddb84786a4a411dfe4587fe0,
title = "NRBP1-Containing CRL2/CRL4A Regulates Amyloid β Production by Targeting BRI2 and BRI3 for Degradation",
abstract = "Yasukawa et al. demonstrate that BRI2 and BRI3, physiological inhibitors of Aβ production and aggregation, are substrates of NRBP1-ubiquitin ligase. In the presence of TSC22D3 and TSC22D4, a dimer of the substrate receptor NRBP1 assembles into a functional Cul2- and Cul4A-containing heterodimeric CRL through overlapping BC-box and cryptic H-box motifs on NRBP1.",
keywords = "Alzheimer's disease, amyloid β, amyloid-β precursor protein/APP, BRI2/ITM2B, BRI3/ITM2C, CRL, Cullin, E3 ubiquitin ligase, NRBP1, ubiquitination",
author = "Takashi Yasukawa and Aya Tsutsui and Chieri Tomomori-Sato and Shigeo Sato and Anita Saraf and Washburn, {Michael P.} and Laurence Florens and Tohru Terada and Kentaro Shimizu and Conaway, {Ronald C.} and Conaway, {Joan W.} and Teijiro Aso",
note = "Funding Information: We thank Dr. Yukiko Yoshida for HA-TR-TUBE plasmid, Dr. Takumi Kamura for pCI-neo-HA-Cul2 and pcDNA3-HA-Cul4A, Dr. Yue Xiong for pcDNA3-Myc-Cul2 and pcDNA3-Myc-Cul4A, Dr. Toshio Kitamura for pMXs-IP-TSC22D1-1 and pMXs-IP-TSC22D3, and Dr. Takako Niikura for F11 cell line. We are also grateful to Dr. Shigetaka Kitajima for providing various equipment and reagents and Dr. Masayuki Tsuda for technical support for animal experiments. This work was supported by JSPS KAKENHI (24590279, 15K08177, and 18K06855 to T.Y.; 24590357, 15K08279, and 18K06959 to T.A.); the Life Science Foundation of Japan (T.Y.); the Mitsui Sumitomo Insurance Welfare Foundation of Japan (T.A.); the Kochi University Hospital Director's Discretionary Expense Research Grant (T.A.); funds from the Stowers Institute for Medical Research, United States (R.C.C. and J.W.C.); and the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from AMED, Japan (JP18am0101107). T.Y. R.C.C. J.W.C. and T.A. designed the study. T.Y. A.T. and T.A. performed experiments and analyzed the data. C.T.-S. and S.S. participated in the study design. A.S. M.P.W. and L.F. performed mass spectrometry data collection and processing. T.T. and K.S. performed modeling and analysis of the complex structures. J.W.C. R.C.C. and T.A. wrote the manuscript with contributions from T.Y. A.S. and T.T. All authors discussed the results and commented on the manuscript. The authors declare no competing interests. Funding Information: We thank Dr. Yukiko Yoshida for HA-TR-TUBE plasmid, Dr. Takumi Kamura for pCI-neo-HA-Cul2 and pcDNA3-HA-Cul4A, Dr. Yue Xiong for pcDNA3-Myc-Cul2 and pcDNA3-Myc-Cul4A, Dr. Toshio Kitamura for pMXs-IP-TSC22D1-1 and pMXs-IP-TSC22D3, and Dr. Takako Niikura for F11 cell line. We are also grateful to Dr. Shigetaka Kitajima for providing various equipment and reagents and Dr. Masayuki Tsuda for technical support for animal experiments. This work was supported by JSPS KAKENHI ( 24590279 , 15K08177 , and 18K06855 to T.Y.; 24590357 , 15K08279 , and 18K06959 to T.A.); the Life Science Foundation of Japan (T.Y.); the Mitsui Sumitomo Insurance Welfare Foundation of Japan (T.A.); the Kochi University Hospital Director{\textquoteright}s Discretionary Expense Research Grant (T.A.); funds from the Stowers Institute for Medical Research, United States (R.C.C. and J.W.C.); and the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) from AMED, Japan ( JP18am0101107 ). Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = mar,
day = "10",
doi = "10.1016/j.celrep.2020.02.059",
language = "English (US)",
volume = "30",
pages = "3478--3491.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}