Structure-based engineering of the midnolin-proteasome pathway for targeted protein degradation

Hongyang Wang , Ying Zheng , Tiantian Wang , Xue Zhang , Peipei Wang , Chuancun Wei , Hongyue Li , Quan Wang , Lu Zhang , Xisong Ke , Wenqing Xu

Protein Cell ›› 2026, Vol. 17 ›› Issue (1) : 83 -88.

PDF (2647KB)
Protein Cell ›› 2026, Vol. 17 ›› Issue (1) :83 -88. DOI: 10.1093/procel/pwaf069
Letter
Structure-based engineering of the midnolin-proteasome pathway for targeted protein degradation
Author information +
History +
PDF (2647KB)

Graphical abstract

Cite this article

Download citation ▾
Hongyang Wang, Ying Zheng, Tiantian Wang, Xue Zhang, Peipei Wang, Chuancun Wei, Hongyue Li, Quan Wang, Lu Zhang, Xisong Ke, Wenqing Xu. Structure-based engineering of the midnolin-proteasome pathway for targeted protein degradation. Protein Cell, 2026, 17(1): 83-88 DOI:10.1093/procel/pwaf069

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Békés M , Langley DR , Crews CM PROTAC targeted protein degraders: the past is prologue. Nat Rev Drug Discov 2022; 21: 181– 200.

[2]

Dong Y , Zhang S , Wu Z et al. Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome. Nature 2019; 565: 49– 55.

[3]

Graham TA , Clements WK , Kimelman D et al. The crystal structure of the β-catenin/ICAT complex reveals the inhibitory mechanism of ICAT. Mol Cell 2002; 10: 563– 571.

[4]

Grimson MJ , Coates JC , Reynolds JP et al. Adherens junctions and β-catenin-mediated cell signalling in a non-metazoan organism. Nature 2000; 408: 727– 731.

[5]

Gu X , Nardone C , Kamitaki N et al. The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation. Science 2023; 381: eadh5021.

[6]

Khan S , Zhang X , Lv D et al. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat Med 2019; 25: 1938– 1947.

[7]

Nusse R , Clevers H Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 2017; 169: 985– 999.

[8]

Sampietro J , Dahlberg CL , Cho US et al. Crystal structure of a β-catenin/BCL9/Tcf4 complex. Mol Cell 2006; 24: 293– 300.

[9]

Snyder NA , Silva GM Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response. J Biol Chem 2021; 297: 101077.

[10]

Tsai JM , Nowak RP , Ebert BL et al. Targeted protein degradation: from mechanisms to clinic. Nat Rev Mol Cell Biol 2024; 25: 740– 757.

[11]

Tsukahara M , Suemori H , Noguchi S et al. Novel nucleolar protein, midnolin, is expressed in the mesencephalon during mouse development. Gene 2000; 254: 45– 55.

[12]

Worden EJ , Dong KC , Martin A An AAA motor-driven mechanical switch in Rpn11 controls deubiquitination at the 26s proteasome. Mol Cell 2017; 67: 799– 811.e8.

[13]

Xing Y , Clements WK , Kimelman D et al. Crystal structure of a β-catenin/Axin complex suggests a mechanism for the β-catenin destruction complex. Genes Dev 2003; 17: 2753– 2764.

[14]

Zhao L , Zhao J , Zhong K et al. Targeted protein degradation: mechanisms, strategies and application. Signal Trans Targeted Ther 2022; 7: 113.

RIGHTS & PERMISSIONS

© The Author(s) 2025. Published by Oxford University Press on behalf of Higher Education Press.

PDF (2647KB)

Supplementary files

Supplementary_Materials

30

Accesses

0

Citation

Detail

Sections
Recommended

/