Protein homeostasis (aka, proteostasis) – the equilibrium and optimal biological function of cellular proteins – is crucial for proper cellular functioning; its
imbalance is closely associated with diverse human diseases, including neurodegeneration and cancers.
Maintenance of proteostasis is attained through the coordinated action of the proteolytic machinery that preserve the proteome integrity.
Especially, the critical contribution of ubiquitin-proteasome system(UPS) to cellular proteostasis has been increasingly recognized in recent years.
We strive to understand cellular proteolytic mechanisms and develop new strategies for improving proteostasis by exploiting the UPS.
We are particularly interested in investigating proteasome, the master player in protein degradation,
and critical deubiquitinating enzymes (DUBs) in human pathophysiology.
Our group is trying to develop chemo-genomic methods to modulate the deubiquitinatio n activities acting upstream of and on the proteasome to explore novel deubiquitination biology. By developing new class of chemical proteolytic inducers and DUB inhibitors, we aim to define novel drug targets in protein quality control machinery and ultimately seek for proteolysis-based therapeutic strategies for human health.
Lim YS, Yoo SM, Patil V, Kim HW, Kim HH, Suh B, Park JY,
Jeong NR, Park CH, Ryu JH, Lee BH, Kim P, Lee SH. Orally bioavailable BTK
PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX
mouse models. Blood Adv. 2023 Jan 10;7(1):92-105. doi:
10.1182/bloodadvances.2022008121.
Chung S, Kang MS, Alimbetov DS, Mun GI, Yunn NO, Kim Y, Kim
BG, Wie M, Lee EA, Ra JS, Oh JM, Lee D, Lee K, Kim J, Han SH, Kim KT, Chung WK,
Nam KH, Park J, Lee B, Kim S, Zhao W, Ryu SH, Lee YS, Myung K, Cho Y.
Regulation of BRCA1 stability through the tandem UBX domains of isoleucyl-tRNA
synthetase 1. Nat Commun. 2022 Nov 8;13(1):6732. doi:
10.1038/s41467-022-34612-y.
Tran NN, Lee BH. Functional implication of ubiquitinating
and deubiquitinating mechanisms in TDP-43 proteinopathies. Front Cell Dev
Biol. 2022 Sep 9;10:931968. doi: 10.3389/fcell.2022.931968.
Hung KY, Klumpe S, Eisele M, Elsasser S, Tian G, Sun S, Moroco J, Cheng T, Joshi T, Seibel T, van Dalen D, Feng XH, Lu Y, Ovaa H, Engen J, Lee BH#, Rudack T#, Sakata E#, and Finley D# (2022) Allosteric control of Ubp6 and the proteasome via a bidirectional switch. Nat. Commun. 13(1):838. doi: 10.1038/s41467-022-28186-y (# Co-corresponding authors).
Ryu HY, Kim LE, Jeong H, Yeo BK, Lee JW, Nam H, Ha S, An HK, Park H, Jung S, Chung KM, Kim J, Lee BH, Cheong H, Kim EK, Yu SW (2021) GSK3B induces autophagy by phosphorylating ULK1. Exp. Mol. Med. 53(3):369-383. doi: 10.1038/s12276-021-00570-6.
Cha IJ, Lee D, Park SS, Chung CG, Kim SY, Jo MG, Kim SY, Lee BH, Lee YS, Lee SB (2020) Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons. Mol. Cells 43(10):870-879. doi: 10.14348/molcells.2020.0158.
Shin JY, Muniyappan S, Tran NN, Park H, Lee SB, and Lee BH (2020) Deubiquitination Reactions on the Proteasome for Proteasome Versatility. Int. J. Mol. Sci. Jul 27;21(15):E5312. doi: 10.3390/ijms21155312.
Kim MH, Jeon J, Lee S, Lee JH, Gao L, Lee BH, Park JM, Kim
YJ, Kwak JM. Proteasome subunit RPT2a promotes PTGS through repressing RNA
quality control in Arabidopsis. Nat Plants. 2019 Dec;5(12):1273-1282.
doi: 10.1038/s41477-019-0546-1. Epub 2019 Nov 18.