Caught the''Catch''of midnolin:structural basis for broad substrate specificity in ubiquitin-independent proteasomal degradationOA
Protein homeostasis serves as the foundation for every cellular decision-division,differentiation,stress adaptation,or death-by precisely balancing the proteome across abundance,quality,spatial distribution,and temporal dynamics;its dysregulation drives numerous human pathologies,including cancers and neurological disorders[1-3].In the traditional ubiquitin-dependent degradation cascade,target proteins are marked by covalent attachment of polyubiquitin chains,a process requiring E1 activating enzymes,E2 conjugating enzymes,and E3 ligases that confer substrate specificity.This ubiquitin signal is then recognized by the 19S regulatory particle of the proteasome,which unfolds and translocates the tagged protein into the 20s core for proteolytic destruction[3].
Chuanyin Li;Ronggui Hu
Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention,China National Ministry of Education,Key Laboratory of Molecular Biology in Medical Sciences,Zhejiang Province,China),the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China Center for Medical Research and Innovation in Digestive System Tumors,Ministry of Education,Hangzhou 310009,ChinaDepartment of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention,China National Ministry of Education,Key Laboratory of Molecular Biology in Medical Sciences,Zhejiang Province,China),the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China Center for Medical Research and Innovation in Digestive System Tumors,Ministry of Education,Hangzhou 310009,China Liangzhu Laboratory,M0E Frontier Science Center for Brain Science and Brain-Machine Integration,State Key Laboratory of Brain-Machine Intelligence,Zhejiang University,Hangzhou 310009,China
生物科学
e conjugating enzymescovalent attachment polyubiquitin chainsaprotein homeostasisneurological disordersproteasomal degradationsubstrate specificityubiquitin independent degradatione activating enzymes
《Acta Biochimica et Biophysica Sinica》 2026 (6)
P.1431-1432,2
supported by the grants from the National Natural Science Foundation of China(Nos.92253302,82200667 and 31900804)the National Science and Technology Innovation 2030 Major Project of China(No.2021ZD0203900)。
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